diff --git a/setup.py b/setup.py
index 3b3d0974542..6a05643838b 100644
--- a/setup.py
+++ b/setup.py
@@ -898,8 +898,11 @@ class PyBuildExt(build_ext):
         blake2_deps.append('hashlib.h')
 
         blake2_macros = []
-        if not cross_compiling and os.uname().machine == "x86_64":
-            # Every x86_64 machine has at least SSE2.
+        if (not cross_compiling and
+                os.uname().machine == "x86_64" and
+                sys.maxsize >  2**32):
+            # Every x86_64 machine has at least SSE2.  Check for sys.maxsize
+            # in case that kernel is 64-bit but userspace is 32-bit.
             blake2_macros.append(('BLAKE2_USE_SSE', '1'))
 
         exts.append( Extension('_blake2',