diff --git a/3rdparty/python/lockfiles/user_reqs.txt b/3rdparty/python/lockfiles/user_reqs.txt
index 3ad594c917c..3321e75861b 100644
--- a/3rdparty/python/lockfiles/user_reqs.txt
+++ b/3rdparty/python/lockfiles/user_reqs.txt
@@ -5,7 +5,7 @@
 # --- BEGIN PANTS LOCKFILE METADATA: DO NOT EDIT OR REMOVE ---
 # {
 #   "version": 1,
-#   "requirements_invalidation_digest": "6adf6599ccc90c6aad4cc62333b089eea937311f47ae9eab025203d7a0e0eb2c",
+#   "requirements_invalidation_digest": "2570870f165f546315ceb7ba2667cc764def9348baf7002ddb0a81c831cfd0fa",
 #   "valid_for_interpreter_constraints": [
 #     "CPython<3.10,>=3.7"
 #   ]
@@ -113,9 +113,9 @@ iniconfig==1.1.1; python_version >= "3.6" \
 packaging==21.0; python_version >= "3.6" \
     --hash=sha256:c86254f9220d55e31cc94d69bade760f0847da8000def4dfe1c6b872fd14ff14 \
     --hash=sha256:7dc96269f53a4ccec5c0670940a4281106dd0bb343f47b7471f779df49c2fbe7
-pex==2.1.48; (python_version >= "2.7" and python_full_version < "3.0.0") or (python_full_version >= "3.5.0" and python_version < "3.10") \
-    --hash=sha256:903ab1e2781dbf077e9936d6a5dada9fa868c5416423065eee7bd00d94f2ea06 \
-    --hash=sha256:5f6a489075c5bbecdb36a42249cd52cfd882e205242f80a1f1e2294951ab46e7
+pex==2.1.49; (python_version >= "2.7" and python_full_version < "3.0.0") or (python_full_version >= "3.5.0" and python_version < "3.10") \
+    --hash=sha256:da3bb92e82906f805c9207d91f2688635028e3900cf1f4a6014c2aa95535d925 \
+    --hash=sha256:af536388eeede93111d8ef0af4a80cbb3d847c1a1470c6f34f3abe83deac1b91
 pluggy==1.0.0; python_version >= "3.6" \
     --hash=sha256:74134bbf457f031a36d68416e1509f34bd5ccc019f0bcc952c7b909d06b37bd3 \
     --hash=sha256:4224373bacce55f955a878bf9cfa763c1e360858e330072059e10bad68531159
diff --git a/3rdparty/python/requirements.txt b/3rdparty/python/requirements.txt
index 9529ea203a2..b35427ed90c 100644
--- a/3rdparty/python/requirements.txt
+++ b/3rdparty/python/requirements.txt
@@ -8,7 +8,7 @@ humbug==0.2.6
 
 ijson==3.1.4
 packaging==21.0
-pex==2.1.48
+pex==2.1.49
 psutil==5.8.0
 pystache==0.5.4
 # This should be kept in sync with `pytest.py`.
diff --git a/src/python/pants/backend/python/subsystems/lambdex_lockfile.txt b/src/python/pants/backend/python/subsystems/lambdex_lockfile.txt
index 84714249f2c..1e6de50b28c 100644
--- a/src/python/pants/backend/python/subsystems/lambdex_lockfile.txt
+++ b/src/python/pants/backend/python/subsystems/lambdex_lockfile.txt
@@ -15,6 +15,6 @@
 lambdex==0.1.6; (python_version >= "2.7" and python_full_version < "3.0.0") or (python_full_version >= "3.6.0" and python_version < "3.10") \
     --hash=sha256:cb685b106617fbd1afd26d6e9472b2e0c99df8574c6d358aee4e6c13aeef8eb1 \
     --hash=sha256:6d1a95c8a31baa703edece8e36a705045b0203c7e886812c27a4dd945aa694e0
-pex==2.1.48; python_version >= "2.7" and python_full_version < "3.0.0" or python_full_version >= "3.6.0" and python_version < "3.10" \
-    --hash=sha256:903ab1e2781dbf077e9936d6a5dada9fa868c5416423065eee7bd00d94f2ea06 \
-    --hash=sha256:5f6a489075c5bbecdb36a42249cd52cfd882e205242f80a1f1e2294951ab46e7
+pex==2.1.49; python_version >= "2.7" and python_full_version < "3.0.0" or python_full_version >= "3.6.0" and python_version < "3.10" \
+    --hash=sha256:da3bb92e82906f805c9207d91f2688635028e3900cf1f4a6014c2aa95535d925 \
+    --hash=sha256:af536388eeede93111d8ef0af4a80cbb3d847c1a1470c6f34f3abe83deac1b91
diff --git a/src/python/pants/backend/python/util_rules/pex_cli.py b/src/python/pants/backend/python/util_rules/pex_cli.py
index 15723fa8b79..aa18ea9c396 100644
--- a/src/python/pants/backend/python/util_rules/pex_cli.py
+++ b/src/python/pants/backend/python/util_rules/pex_cli.py
@@ -37,9 +37,9 @@ class PexBinary(TemplatedExternalTool):
     name = "pex"
     help = "The PEX (Python EXecutable) tool (https://github.com/pantsbuild/pex)."
 
-    default_version = "v2.1.48"
+    default_version = "v2.1.49"
     default_url_template = "https://github.com/pantsbuild/pex/releases/download/{version}/pex"
-    version_constraints = ">=2.1.48,<3.0"
+    version_constraints = ">=2.1.49,<3.0"
 
     @classproperty
     def default_known_versions(cls):
@@ -48,8 +48,8 @@ def default_known_versions(cls):
                 (
                     cls.default_version,
                     plat,
-                    "4f86bc7e9e852fe59f9bc774d910b60c7f1df5a194ba0bdf491f70ba78a2e6bb",
-                    "3640820",
+                    "6fbee0df046793b555f5225490081ae44893c75d51024e7e976d4427bf914527",
+                    "3640830",
                 )
             )
             for plat in ["macos_arm64", "macos_x86_64", "linux_x86_64"]