diff --git a/src/python/pants/backend/python/goals/lockfile.py b/src/python/pants/backend/python/goals/lockfile.py
index 5d1326222c7..fc8f19435aa 100644
--- a/src/python/pants/backend/python/goals/lockfile.py
+++ b/src/python/pants/backend/python/goals/lockfile.py
@@ -37,6 +37,7 @@
 from pants.engine.process import ProcessCacheScope, ProcessResult
 from pants.engine.rules import Get, MultiGet, collect_rules, goal_rule, rule
 from pants.engine.unions import UnionMembership, union
+from pants.python.python_repos import PythonRepos
 from pants.util.logging import LogLevel
 from pants.util.ordered_set import FrozenOrderedSet
 
@@ -69,7 +70,7 @@ def register_options(cls, register) -> None:
                 "generate the lockfile for those two tools.\n\n"
                 "If you specify an invalid resolve name, like 'fake', Pants will output all "
                 "possible values.\n\n"
-                "If not specified, will generate for all resolves."
+                "If not specified, Pants will generate for all resolves."
             ),
         )
         register(
@@ -245,7 +246,13 @@ async def generate_lockfiles_goal(
     workspace: Workspace,
     union_membership: UnionMembership,
     generate_lockfiles_subsystem: GenerateLockfilesSubsystem,
+    python_repos: PythonRepos,
 ) -> GenerateLockfilesGoal:
+    if python_repos.repos:
+        warn_python_repos("repos")
+    if python_repos.indexes != [python_repos.pypi_index]:
+        warn_python_repos("indexes")
+
     specified_tool_requests = await MultiGet(
         Get(PythonLockfileRequest, PythonToolLockfileSentinel, sentinel())
         for sentinel in determine_tool_sentinels_to_generate(
@@ -269,6 +276,19 @@ async def generate_lockfiles_goal(
     return GenerateLockfilesGoal(exit_code=0)
 
 
+def warn_python_repos(option: str) -> None:
+    logger.warning(
+        f"The option `[python-repos].{option}` is configured, but it does not currently work "
+        "with lockfile generation. Lockfile generation will fail if the relevant requirements "
+        "cannot be located on PyPI.\n\n"
+        "If lockfile generation fails, you can disable lockfiles by setting "
+        "`[tool].lockfile = '<none>'`, e.g. setting `[black].lockfile`. You can also manually "
+        "generate a lockfile, such as by using pip-compile or `pip freeze`. Set the "
+        "`[tool].lockfile` option to the path you manually generated. When manually maintaining "
+        "lockfiles, set `[python-setup].invalid_lockfile_behavior = 'ignore'."
+    )
+
+
 class UnrecognizedResolveNamesError(Exception):
     pass
 
diff --git a/src/python/pants/backend/python/subsystems/python_tool_base.py b/src/python/pants/backend/python/subsystems/python_tool_base.py
index ad68a5c4e22..fbf2dab1db7 100644
--- a/src/python/pants/backend/python/subsystems/python_tool_base.py
+++ b/src/python/pants/backend/python/subsystems/python_tool_base.py
@@ -110,7 +110,11 @@ def register_options(cls, register):
                     "To use a custom lockfile, set this option to a file path relative to the "
                     f"build root, then run `./pants generate-lockfiles "
                     f"--resolve={cls.options_scope}`.\n\n"
-                    ""
+                    "Lockfile generation currently does not wire up the `[python-repos]` options. "
+                    "If lockfile generation fails, you can manually generate a lockfile, such as "
+                    "by using pip-compile or `pip freeze`. Set this option to the path to your "
+                    "manually generated lockfile. When manually maintaining lockfiles, set "
+                    "`[python-setup].invalid_lockfile_behavior = 'ignore'`."
                 ),
             )
 
diff --git a/src/python/pants/python/python_repos.py b/src/python/pants/python/python_repos.py
index 476ec968efb..1c6988ae7c0 100644
--- a/src/python/pants/python/python_repos.py
+++ b/src/python/pants/python/python_repos.py
@@ -13,6 +13,8 @@ class PythonRepos(Subsystem):
         "custom cheeseshops when resolving requirements."
     )
 
+    pypi_index = "https://pypi.org/simple/"
+
     @classmethod
     def register_options(cls, register):
         super().register_options(register)
@@ -30,7 +32,7 @@ def register_options(cls, register):
             "--indexes",
             advanced=True,
             type=list,
-            default=["https://pypi.org/simple/"],
+            default=[cls.pypi_index],
             help=(
                 "URLs of code repository indexes to look for requirements. If set to an empty "
                 "list, then Pex will use no indices (meaning it will not use PyPI). The values "