diff --git a/pex/vendor/__init__.py b/pex/vendor/__init__.py
index dd6e7e428..0f81e0057 100644
--- a/pex/vendor/__init__.py
+++ b/pex/vendor/__init__.py
@@ -207,19 +207,24 @@ def iter_vendor_specs(filter_requires_python=None):
     # We shell out to pip at buildtime to resolve and install dependencies.
     # N.B.: We're currently using a patched version of Pip 20.3.4 housed at
     # https://github.com/pex-tool/pip/tree/pex/patches/generation-2.
-    # It has 2 patches:
+    # It has 3 patches:
     # 1.) https://github.com/pex-tool/pip/commit/06f462537c981116c763c1ba40cf40e9dd461bcf
     #     The patch works around a bug in `pip download --constraint...` tracked at
     #     https://github.com/pypa/pip/issues/9283 and fixed by https://github.com/pypa/pip/pull/9301
     #     there and https://github.com/pex-tool/pip/pull/8 in our fork.
     # 2.) https://github.com/pex-tool/pip/commit/386a54f097ece66775d0c7f34fd29bb596c6b0be
     #     This is a cherry-pick of
-    #     https://github.com/pex-tool/pip/commit/00fb5a0b224cde08e3e5ca034247baadfb646468
+    #     https://github.com/pypa/pip/commit/00fb5a0b224cde08e3e5ca034247baadfb646468
     #     (https://github.com/pypa/pip/pull/9533) from upstream that upgrades Pip's vendored
     #     packaging to 20.9 to pick up support for mac universal2 wheels.
+    # 3.) https://github.com/pex-tool/pip/commit/00827ec9f4275a7786425cf006466c56f4cbd862
+    #     This is a cherry-pick of
+    #     https://github.com/pypa/pip/commit/601bcf82eccfbc15c1ff6cc735aafb2c9dab81a5
+    #     (https://github.com/pypa/pip/pull/12716) from upstream that fixes glibc version probing on
+    #     musl libc systems.
     yield VendorSpec.git(
         repo="https://github.com/pex-tool/pip",
-        commit="386a54f097ece66775d0c7f34fd29bb596c6b0be",
+        commit="00827ec9f4275a7786425cf006466c56f4cbd862",
         project_name="pip",
         rewrite=False,
     )
diff --git a/pex/vendor/_vendored/pip/.layout.json b/pex/vendor/_vendored/pip/.layout.json
index e30534fe3..48d545b25 100644
--- a/pex/vendor/_vendored/pip/.layout.json
+++ b/pex/vendor/_vendored/pip/.layout.json
@@ -1 +1 @@
-{"fingerprint": "120267325b80f5c4b4adac019eb6617ab3319395c043d2871eedf70dd6ae2954", "record_relpath": "pip-20.3.4.dist-info/RECORD", "root_is_purelib": true, "stash_dir": ".prefix"}
\ No newline at end of file
+{"fingerprint": "23b678435eebb1c7423541b5663bdc518833a4b75a3a3a2192466a37cd7b1861", "record_relpath": "pip-20.3.4.dist-info/RECORD", "root_is_purelib": true, "stash_dir": ".prefix"}
\ No newline at end of file
diff --git a/pex/vendor/_vendored/pip/pip/_internal/utils/glibc.py b/pex/vendor/_vendored/pip/pip/_internal/utils/glibc.py
index 361042441..fb65d32c5 100644
--- a/pex/vendor/_vendored/pip/pip/_internal/utils/glibc.py
+++ b/pex/vendor/_vendored/pip/pip/_internal/utils/glibc.py
@@ -49,7 +49,20 @@ def glibc_version_string_ctypes():
     # manpage says, "If filename is NULL, then the returned handle is for the
     # main program". This way we can let the linker do the work to figure out
     # which libc our process is actually using.
-    process_namespace = ctypes.CDLL(None)
+    #
+    # We must also handle the special case where the executable is not a
+    # dynamically linked executable. This can occur when using musl libc,
+    # for example. In this situation, dlopen() will error, leading to an
+    # OSError. Interestingly, at least in the case of musl, there is no
+    # errno set on the OSError. The single string argument used to construct
+    # OSError comes from libc itself and is therefore not portable to
+    # hard code here. In any case, failure to call dlopen() means we
+    # can't proceed, so we bail on our attempt.
+    try:
+        process_namespace = ctypes.CDLL(None)
+    except OSError:
+        return None
+
     try:
         gnu_get_libc_version = process_namespace.gnu_get_libc_version
     except AttributeError:
diff --git a/tests/integration/test_issue_2017.py b/tests/integration/test_issue_2017.py
new file mode 100644
index 000000000..468d4f61c
--- /dev/null
+++ b/tests/integration/test_issue_2017.py
@@ -0,0 +1,76 @@
+# Copyright 2024 Pex project contributors.
+# Licensed under the Apache License, Version 2.0 (see LICENSE).
+
+from __future__ import absolute_import
+
+import os.path
+import shutil
+import subprocess
+import tarfile
+from textwrap import dedent
+
+import pytest
+
+from pex.common import is_exe, safe_open
+from pex.compatibility import urlparse
+from pex.fetcher import URLFetcher
+from pex.pep_440 import Version
+from pex.pip.version import PipVersion
+from pex.typing import TYPE_CHECKING
+from testing import IS_LINUX, run_pex_command
+
+if TYPE_CHECKING:
+    from typing import Any
+
+
+# TODO(John Sirois): Include a test of >= Pip 24.2 when Pex adds support for it.
+#  See: https://github.com/pex-tool/pex/issues/2471
+@pytest.mark.skipif(
+    PipVersion.DEFAULT > PipVersion.VENDORED and PipVersion.DEFAULT.version < Version("24.2"),
+    reason=(
+        "Although Pex's vendored Pip is patched to handle statically linked musl libc CPython, no "
+        "version of Pip Pex supports handles these Pythons until Pip 24.2"
+    ),
+)
+@pytest.mark.skipif(
+    not IS_LINUX,
+    reason="This test tests statically linked musl libc CPython which is only available for Linux.",
+)
+def test_statically_linked_musl_libc_cpython_support(tmpdir):
+    # type: (Any) -> None
+
+    pbs_distribution_url = (
+        "https://github.com/indygreg/python-build-standalone/releases/download/20221220/"
+        "cpython-3.10.9+20221220-x86_64_v3-unknown-linux-musl-install_only.tar.gz"
+    )
+    pbs_distribution = os.path.join(
+        str(tmpdir),
+        os.path.basename(urlparse.urlparse(pbs_distribution_url).path),
+    )
+    with URLFetcher().get_body_stream(pbs_distribution_url) as read_fp, open(
+        pbs_distribution, "wb"
+    ) as write_fp:
+        shutil.copyfileobj(read_fp, write_fp)
+    with tarfile.open(pbs_distribution) as tf:
+        tf.extractall(str(tmpdir))
+    statically_linked_musl_libc_cpython = os.path.join(str(tmpdir), "python", "bin", "python3")
+    assert is_exe(statically_linked_musl_libc_cpython)
+
+    pex = os.path.join(str(tmpdir), "pex")
+    run_pex_command(
+        args=["fortune==1.1.1", "-c", "fortune", "-o", pex],
+        python=statically_linked_musl_libc_cpython,
+    ).assert_success()
+
+    fortune_db = os.path.join(str(tmpdir), "fortunes")
+    with safe_open(fortune_db, "w") as fp:
+        fp.write(
+            dedent(
+                """\
+                A day for firm decisions!!!!!  Or is it?
+                %
+                """
+            )
+        )
+    output = subprocess.check_output(args=[pex, fortune_db])
+    assert b"A day for firm decisions!!!!!  Or is it?\n" == output, output.decode("utf-8")