diff --git a/Doc/whatsnew/3.8.rst b/Doc/whatsnew/3.8.rst
index 2de7a50a471..a9b689d5372 100644
--- a/Doc/whatsnew/3.8.rst
+++ b/Doc/whatsnew/3.8.rst
@@ -131,6 +131,10 @@ Optimizations
   objects (e.g. tuple, list, dict) size is reduced 4 or 8 bytes.
   (Contributed by Inada Naoki in :issue:`33597`)
 
+* :class:`uuid.UUID` now uses ``__slots__`` to reduce its memory footprint.
+  Note that this means that instances can no longer be weak-referenced and
+  that arbitrary attributes can no longer be added to them.
+
 
 Build and C API Changes
 =======================
@@ -275,6 +279,9 @@ Changes in the Python API
 * The function :func:`math.factorial` no longer accepts arguments that are not
   int-like. (Contributed by Pablo Galindo in :issue:`33083`.)
 
+* :class:`uuid.UUID` now uses ``__slots__``, therefore instances can no longer
+  be weak-referenced and attributes can no longer be added.
+
 
 CPython bytecode changes
 ------------------------
diff --git a/Lib/test/test_uuid.py b/Lib/test/test_uuid.py
index 9ec59d51957..c1b35c4a7f6 100644
--- a/Lib/test/test_uuid.py
+++ b/Lib/test/test_uuid.py
@@ -2,6 +2,8 @@ import unittest.mock
 from test import support
 import builtins
 import contextlib
+import copy
+from functools import partial
 import io
 import os
 import pickle
@@ -313,63 +315,139 @@ class BaseTestUUID:
         node2 = self.uuid.getnode()
         self.assertEqual(node1, node2, '%012x != %012x' % (node1, node2))
 
-    def _setup_for_pickle(self):
-        orig_uuid = sys.modules.get('uuid')
-        sys.modules['uuid'] = self.uuid
-
-        def restore_uuid_module():
-            if orig_uuid is not None:
-                sys.modules['uuid'] = orig_uuid
-            else:
-                del sys.modules['uuid']
-        self.addCleanup(restore_uuid_module)
-
     def test_pickle_roundtrip(self):
-        self._setup_for_pickle()
+        def check(actual, expected):
+            self.assertEqual(actual, expected)
+            self.assertEqual(actual.is_safe, expected.is_safe)
 
-        u = self.uuid.UUID('12345678123456781234567812345678')
-        self.assertEqual(u, pickle.loads(pickle.dumps(u)))
+        with support.swap_item(sys.modules, 'uuid', self.uuid):
+            for is_safe in self.uuid.SafeUUID:
+                u = self.uuid.UUID('d82579ce6642a0de7ddf490a7aec7aa5',
+                                   is_safe=is_safe)
+                check(copy.copy(u), u)
+                check(copy.deepcopy(u), u)
+                for proto in range(pickle.HIGHEST_PROTOCOL + 1):
+                    with self.subTest(protocol=proto):
+                        check(pickle.loads(pickle.dumps(u, proto)), u)
 
     def test_unpickle_previous_python_versions(self):
-        self._setup_for_pickle()
+        def check(actual, expected):
+            self.assertEqual(actual, expected)
+            self.assertEqual(actual.is_safe, expected.is_safe)
 
-        u = self.uuid.UUID('12345678123456781234567812345678')
-
-        # Python 2.7 protocol 0-2 pickles of u
-        py27_pickles = [
-            b'ccopy_reg\n_reconstructor\np0\n(cuuid\nUUID\np1\nc__builtin__\nob'
-            b'ject\np2\nNtp3\nRp4\n(dp5\nS\'int\'\np6\nL24197857161011715162171'
-            b'839636988778104L\nsb.',
-            b'ccopy_reg\n_reconstructor\nq\x00(cuuid\nUUID\nq\x01c__builtin__\n'
-            b'object\nq\x02Ntq\x03Rq\x04}q\x05U\x03intq\x06L2419785716101171516'
-            b'2171839636988778104L\nsb.',
-            b'\x80\x02cuuid\nUUID\nq\x00)\x81q\x01}q\x02U\x03intq\x03\x8a\x10xV'
-            b'4\x12xV4\x12xV4\x12xV4\x12sb.',
+        pickled_uuids = [
+            # Python 2.7, protocol 0
+            b'ccopy_reg\n_reconstructor\n(cuuid\nUUID\nc__builtin__\nobject\nN'
+            b'tR(dS\'int\'\nL287307832597519156748809049798316161701L\nsb.',
+            # Python 2.7, protocol 1
+            b'ccopy_reg\n_reconstructor\n(cuuid\nUUID\nc__builtin__\nobject\nN'
+            b'tR}U\x03intL287307832597519156748809049798316161701L\nsb.',
+            # Python 2.7, protocol 2
+            b'\x80\x02cuuid\nUUID\n)\x81}U\x03int\x8a\x11\xa5z\xecz\nI\xdf}'
+            b'\xde\xa0Bf\xcey%\xd8\x00sb.',
+            # Python 3.6, protocol 0
+            b'ccopy_reg\n_reconstructor\n(cuuid\nUUID\nc__builtin__\nobject\nN'
+            b'tR(dVint\nL287307832597519156748809049798316161701L\nsb.',
+            # Python 3.6, protocol 1
+            b'ccopy_reg\n_reconstructor\n(cuuid\nUUID\nc__builtin__\nobject\nN'
+            b'tR}X\x03\x00\x00\x00intL287307832597519156748809049798316161701L'
+            b'\nsb.',
+            # Python 3.6, protocol 2
+            b'\x80\x02cuuid\nUUID\n)\x81}X\x03\x00\x00\x00int\x8a\x11\xa5z\xec'
+            b'z\nI\xdf}\xde\xa0Bf\xcey%\xd8\x00sb.',
+            # Python 3.6, protocol 3
+            b'\x80\x03cuuid\nUUID\n)\x81}X\x03\x00\x00\x00int\x8a\x11\xa5z\xec'
+            b'z\nI\xdf}\xde\xa0Bf\xcey%\xd8\x00sb.',
+            # Python 3.6, protocol 4
+            b'\x80\x04\x95+\x00\x00\x00\x00\x00\x00\x00\x8c\x04uuid\x8c\x04UUI'
+            b'D\x93)\x81}\x8c\x03int\x8a\x11\xa5z\xecz\nI\xdf}\xde\xa0Bf\xcey%'
+            b'\xd8\x00sb.',
+            # Python 3.7, protocol 0
+            b'ccopy_reg\n_reconstructor\n(cuuid\nUUID\nc__builtin__\nobject\nN'
+            b'tR(dVint\nL287307832597519156748809049798316161701L\nsVis_safe\n'
+            b'cuuid\nSafeUUID\n(NtRsb.',
+            # Python 3.7, protocol 1
+            b'ccopy_reg\n_reconstructor\n(cuuid\nUUID\nc__builtin__\nobject\nN'
+            b'tR}(X\x03\x00\x00\x00intL287307832597519156748809049798316161701'
+            b'L\nX\x07\x00\x00\x00is_safecuuid\nSafeUUID\n(NtRub.',
+            # Python 3.7, protocol 2
+            b'\x80\x02cuuid\nUUID\n)\x81}(X\x03\x00\x00\x00int\x8a\x11\xa5z'
+            b'\xecz\nI\xdf}\xde\xa0Bf\xcey%\xd8\x00X\x07\x00\x00\x00is_safecuu'
+            b'id\nSafeUUID\nN\x85Rub.',
+            # Python 3.7, protocol 3
+            b'\x80\x03cuuid\nUUID\n)\x81}(X\x03\x00\x00\x00int\x8a\x11\xa5z'
+            b'\xecz\nI\xdf}\xde\xa0Bf\xcey%\xd8\x00X\x07\x00\x00\x00is_safecuu'
+            b'id\nSafeUUID\nN\x85Rub.',
+            # Python 3.7, protocol 4
+            b'\x80\x04\x95F\x00\x00\x00\x00\x00\x00\x00\x8c\x04uuid\x94\x8c'
+            b'\x04UUID\x93)\x81}(\x8c\x03int\x8a\x11\xa5z\xecz\nI\xdf}\xde\xa0'
+            b'Bf\xcey%\xd8\x00\x8c\x07is_safeh\x00\x8c\x08SafeUUID\x93N\x85Rub'
+            b'.',
         ]
-        # Python 3.6 protocol 0-4 pickles of u
-        py36_pickles = [
-            b'ccopy_reg\n_reconstructor\np0\n(cuuid\nUUID\np1\nc__builtin__\nob'
-            b'ject\np2\nNtp3\nRp4\n(dp5\nVint\np6\nL241978571610117151621718396'
-            b'36988778104L\nsb.',
-            b'ccopy_reg\n_reconstructor\nq\x00(cuuid\nUUID\nq\x01c__builtin__\n'
-            b'object\nq\x02Ntq\x03Rq\x04}q\x05X\x03\x00\x00\x00intq\x06L2419785'
-            b'7161011715162171839636988778104L\nsb.',
-            b'\x80\x02cuuid\nUUID\nq\x00)\x81q\x01}q\x02X\x03\x00\x00\x00intq'
-            b'\x03\x8a\x10xV4\x12xV4\x12xV4\x12xV4\x12sb.',
-            b'\x80\x03cuuid\nUUID\nq\x00)\x81q\x01}q\x02X\x03\x00\x00\x00intq'
-            b'\x03\x8a\x10xV4\x12xV4\x12xV4\x12xV4\x12sb.',
-            b'\x80\x04\x950\x00\x00\x00\x00\x00\x00\x00\x8c\x04uuid\x94\x8c\x04'
-            b'UUID\x94\x93\x94)\x81\x94}\x94\x8c\x03int\x94\x8a\x10xV4\x12xV4'
-            b'\x12xV4\x12xV4\x12sb.',
+        pickled_uuids_safe = [
+            # Python 3.7, protocol 0
+            b'ccopy_reg\n_reconstructor\n(cuuid\nUUID\nc__builtin__\nobject\nN'
+            b'tR(dVint\nL287307832597519156748809049798316161701L\nsVis_safe\n'
+            b'cuuid\nSafeUUID\n(I0\ntRsb.',
+            # Python 3.7, protocol 1
+            b'ccopy_reg\n_reconstructor\n(cuuid\nUUID\nc__builtin__\nobject\nN'
+            b'tR}(X\x03\x00\x00\x00intL287307832597519156748809049798316161701'
+            b'L\nX\x07\x00\x00\x00is_safecuuid\nSafeUUID\n(K\x00tRub.',
+            # Python 3.7, protocol 2
+            b'\x80\x02cuuid\nUUID\n)\x81}(X\x03\x00\x00\x00int\x8a\x11\xa5z'
+            b'\xecz\nI\xdf}\xde\xa0Bf\xcey%\xd8\x00X\x07\x00\x00\x00is_safecuu'
+            b'id\nSafeUUID\nK\x00\x85Rub.',
+            # Python 3.7, protocol 3
+            b'\x80\x03cuuid\nUUID\n)\x81}(X\x03\x00\x00\x00int\x8a\x11\xa5z'
+            b'\xecz\nI\xdf}\xde\xa0Bf\xcey%\xd8\x00X\x07\x00\x00\x00is_safecuu'
+            b'id\nSafeUUID\nK\x00\x85Rub.',
+            # Python 3.7, protocol 4
+            b'\x80\x04\x95G\x00\x00\x00\x00\x00\x00\x00\x8c\x04uuid\x94\x8c'
+            b'\x04UUID\x93)\x81}(\x8c\x03int\x8a\x11\xa5z\xecz\nI\xdf}\xde\xa0'
+            b'Bf\xcey%\xd8\x00\x8c\x07is_safeh\x00\x8c\x08SafeUUID\x93K\x00'
+            b'\x85Rub.',
+        ]
+        pickled_uuids_unsafe = [
+            # Python 3.7, protocol 0
+            b'ccopy_reg\n_reconstructor\n(cuuid\nUUID\nc__builtin__\nobject\nN'
+            b'tR(dVint\nL287307832597519156748809049798316161701L\nsVis_safe\n'
+            b'cuuid\nSafeUUID\n(I-1\ntRsb.',
+            # Python 3.7, protocol 1
+            b'ccopy_reg\n_reconstructor\n(cuuid\nUUID\nc__builtin__\nobject\nN'
+            b'tR}(X\x03\x00\x00\x00intL287307832597519156748809049798316161701'
+            b'L\nX\x07\x00\x00\x00is_safecuuid\nSafeUUID\n(J\xff\xff\xff\xfftR'
+            b'ub.',
+            # Python 3.7, protocol 2
+            b'\x80\x02cuuid\nUUID\n)\x81}(X\x03\x00\x00\x00int\x8a\x11\xa5z'
+            b'\xecz\nI\xdf}\xde\xa0Bf\xcey%\xd8\x00X\x07\x00\x00\x00is_safecuu'
+            b'id\nSafeUUID\nJ\xff\xff\xff\xff\x85Rub.',
+            # Python 3.7, protocol 3
+            b'\x80\x03cuuid\nUUID\n)\x81}(X\x03\x00\x00\x00int\x8a\x11\xa5z'
+            b'\xecz\nI\xdf}\xde\xa0Bf\xcey%\xd8\x00X\x07\x00\x00\x00is_safecuu'
+            b'id\nSafeUUID\nJ\xff\xff\xff\xff\x85Rub.',
+            # Python 3.7, protocol 4
+            b'\x80\x04\x95J\x00\x00\x00\x00\x00\x00\x00\x8c\x04uuid\x94\x8c'
+            b'\x04UUID\x93)\x81}(\x8c\x03int\x8a\x11\xa5z\xecz\nI\xdf}\xde\xa0'
+            b'Bf\xcey%\xd8\x00\x8c\x07is_safeh\x00\x8c\x08SafeUUID\x93J\xff'
+            b'\xff\xff\xff\x85Rub.',
         ]
 
-        for pickled in py27_pickles + py36_pickles:
-            unpickled = pickle.loads(pickled)
-            self.assertEqual(unpickled, u)
-            # is_safe was added in 3.7.  When unpickling values from older
-            # versions, is_safe will be missing, so it should be set to
-            # SafeUUID.unknown.
-            self.assertEqual(unpickled.is_safe, self.uuid.SafeUUID.unknown)
+        u = self.uuid.UUID('d82579ce6642a0de7ddf490a7aec7aa5')
+        u_safe = self.uuid.UUID('d82579ce6642a0de7ddf490a7aec7aa5',
+                                is_safe=self.uuid.SafeUUID.safe)
+        u_unsafe = self.uuid.UUID('d82579ce6642a0de7ddf490a7aec7aa5',
+                                  is_safe=self.uuid.SafeUUID.unsafe)
+
+        with support.swap_item(sys.modules, 'uuid', self.uuid):
+            for pickled in pickled_uuids:
+                # is_safe was added in 3.7.  When unpickling values from older
+                # versions, is_safe will be missing, so it should be set to
+                # SafeUUID.unknown.
+                check(pickle.loads(pickled), u)
+            for pickled in pickled_uuids_safe:
+                check(pickle.loads(pickled), u_safe)
+            for pickled in pickled_uuids_unsafe:
+                check(pickle.loads(pickled), u_unsafe)
 
     # bpo-32502: UUID1 requires a 48-bit identifier, but hardware identifiers
     # need not necessarily be 48 bits (e.g., EUI-64).
diff --git a/Lib/uuid.py b/Lib/uuid.py
index 51538822151..073ca711ab4 100644
--- a/Lib/uuid.py
+++ b/Lib/uuid.py
@@ -207,26 +207,19 @@ class UUID:
         object.__setattr__(self, 'is_safe', is_safe)
 
     def __getstate__(self):
-        d = {attr: getattr(self, attr) for attr in self.__slots__}
-        # is_safe is a SafeUUID instance.  Return just its value, so that
-        # it can be unpickled in older Python versions without SafeUUID.
-        d['is_safe'] = d['is_safe'].value
+        d = {'int': self.int}
+        if self.is_safe != SafeUUID.unknown:
+            # is_safe is a SafeUUID instance.  Return just its value, so that
+            # it can be un-pickled in older Python versions without SafeUUID.
+            d['is_safe'] = self.is_safe.value
         return d
 
     def __setstate__(self, state):
-        # is_safe was added in 3.7
-        state.setdefault('is_safe', SafeUUID.unknown.value)
-
-        for attr in self.__slots__:
-            value = state[attr]
-
-            # for is_safe, restore the SafeUUID from the stored value
-            if attr == 'is_safe':
-                try:
-                    value = SafeUUID(value)
-                except ValueError:
-                    value = SafeUUID.unknown
-            object.__setattr__(self, attr, value)
+        object.__setattr__(self, 'int', state['int'])
+        # is_safe was added in 3.7; it is also omitted when it is "unknown"
+        object.__setattr__(self, 'is_safe',
+                           SafeUUID(state['is_safe'])
+                           if 'is_safe' in state else SafeUUID.unknown)
 
     def __eq__(self, other):
         if isinstance(other, UUID):