diff --git a/cibuildwheel/macos.py b/cibuildwheel/macos.py
index 9d3b2d15..0285b598 100644
--- a/cibuildwheel/macos.py
+++ b/cibuildwheel/macos.py
@@ -133,6 +133,9 @@ def build(project_dir, output_dir, test_command, test_requires, test_extras, bef
             installation_bin_path,
             env['PATH'],
         ])
+        # Fix issue with site.py setting the wrong `sys.prefix`, `sys.exec_prefix`, `sys.path`, ... for PyPy: https://foss.heptapod.net/pypy/pypy/issues/3175
+        # Be safe and avoid other issues by just always removing the '__PYVENV_LAUNCHER__' environment variable (cfr. https://github.com/python/cpython/pull/9516)
+        env.pop('__PYVENV_LAUNCHER__', None)
         env = environment.as_dictionary(prev_environment=env)
 
         # check what version we're on
@@ -203,7 +206,7 @@ def build(project_dir, output_dir, test_command, test_requires, test_extras, bef
             ])
             # Fix some weird issue with the shebang of installed scripts
             # See https://github.com/theacodes/nox/issues/44 and https://github.com/pypa/virtualenv/issues/620
-            virtualenv_env.pop('__PYVENV_LAUNCHER__', None)
+            # virtualenv_env.pop('__PYVENV_LAUNCHER__', None)  # No need for this anymore, as '__PYVENV_LAUNCHER__' is already removed from `env` above
 
             # check that we are using the Python from the virtual environment
             call(['which', 'python'], env=virtualenv_env)