diff --git a/ddtrace/bootstrap/sitecustomize.py b/ddtrace/bootstrap/sitecustomize.py
index b35419d6648..6c689a5262e 100644
--- a/ddtrace/bootstrap/sitecustomize.py
+++ b/ddtrace/bootstrap/sitecustomize.py
@@ -109,6 +109,7 @@ def drop(module_name):
             "concurrent",
             "typing",
             "re",  # referenced by the typing module
+            "sre_constants",  # imported by re at runtime
             "logging",
             "attr",
             "google.protobuf",  # the upb backend in >= 4.21 does not like being unloaded
diff --git a/releasenotes/notes/fix-re-unload-8770a3d497234243.yaml b/releasenotes/notes/fix-re-unload-8770a3d497234243.yaml
new file mode 100644
index 00000000000..ae19172ad65
--- /dev/null
+++ b/releasenotes/notes/fix-re-unload-8770a3d497234243.yaml
@@ -0,0 +1,5 @@
+---
+fixes:
+  - |
+    Fixed a bug that caused applications using gevent and cassandra to fail to
+    start with the ddtrace-run command.
diff --git a/tests/commands/test_runner.py b/tests/commands/test_runner.py
index 8e34641a3ef..47124f30385 100644
--- a/tests/commands/test_runner.py
+++ b/tests/commands/test_runner.py
@@ -468,3 +468,16 @@ def test_no_args():
     p.wait()
     assert p.returncode == 1
     assert six.b("usage:") in p.stdout.read()
+
+
+@pytest.mark.subprocess(ddtrace_run=True, env=dict(DD_UNLOAD_MODULES_FROM_SITECUSTOMIZE="1"))
+def test_ddtrace_re_module():
+    import re
+
+    re.Scanner(
+        (
+            ("frozen", None),
+            (r"[a-zA-Z0-9_]+", lambda s, t: t),
+            (r"[\s,<>]", None),
+        )
+    )