diff --git a/tests/v1/kv_connector/unit/test_config.py b/tests/v1/kv_connector/unit/test_config.py
index 8a547c3f03f9..821807424575 100644
--- a/tests/v1/kv_connector/unit/test_config.py
+++ b/tests/v1/kv_connector/unit/test_config.py
@@ -65,6 +65,61 @@ def test_kv_connector(
         assert "existing_key" not in kv_connector_extra_config
 
 
+def _build_config(
+    *, kv_connector: str | None, enable_sleep_mode: bool = False
+) -> VllmConfig:
+    """Build a VllmConfig that exercises _verify_kv_transfer_compat without
+    requiring a real model (avoids HF downloads in CI)."""
+    from types import SimpleNamespace
+
+    kv_transfer_config = (
+        KVTransferConfig(kv_connector=kv_connector, kv_role="kv_both")
+        if kv_connector is not None
+        else None
+    )
+    cfg = VllmConfig.__new__(VllmConfig)
+    cfg.kv_transfer_config = kv_transfer_config
+    cfg.model_config = SimpleNamespace(enable_sleep_mode=enable_sleep_mode)
+    cfg._verify_kv_transfer_compat()
+    return cfg
+
+
+@pytest.mark.parametrize(
+    "kv_connector", ["NixlConnector", "MooncakeConnectorV1", "SomeOOTConnector"]
+)
+def test_kv_connector_rejects_expandable_segments(monkeypatch, kv_connector):
+    """KV connectors that pin KV cache memory (e.g. via ibv_reg_mr) are
+    invalidated when expandable_segments lets the CUDA VMM allocator remap
+    the underlying physical pages. We can't enumerate every connector that
+    does this (especially OOT ones), so reject the combination whenever any
+    connector is configured."""
+    monkeypatch.setenv("PYTORCH_CUDA_ALLOC_CONF", "expandable_segments:True")
+    with pytest.raises(ValueError, match="expandable_segments"):
+        _build_config(kv_connector=kv_connector)
+
+
+def test_kv_connector_allows_expandable_segments_with_sleep_mode(monkeypatch):
+    """Sleep mode routes KV allocations through CuMemAllocator's pool, which
+    auto-disables expandable_segments (see #40812)."""
+    monkeypatch.setenv("PYTORCH_CUDA_ALLOC_CONF", "expandable_segments:True")
+    _build_config(kv_connector="NixlConnector", enable_sleep_mode=True)
+
+
+def test_kv_connector_allows_other_alloc_conf(monkeypatch):
+    """Other PYTORCH_CUDA_ALLOC_CONF values must not be rejected."""
+    monkeypatch.setenv(
+        "PYTORCH_CUDA_ALLOC_CONF", "max_split_size_mb:512,expandable_segments:False"
+    )
+    _build_config(kv_connector="NixlConnector")
+
+
+def test_no_kv_connector_ignores_expandable_segments(monkeypatch):
+    """The expandable_segments check only applies when a KV connector is
+    configured."""
+    monkeypatch.setenv("PYTORCH_CUDA_ALLOC_CONF", "expandable_segments:True")
+    _build_config(kv_connector=None)
+
+
 def test_kv_offloading_size_only_uses_native_default():
     """Test that setting only kv_offloading_size enables native offloading."""
     vllm_config = VllmConfig(
diff --git a/vllm/config/vllm.py b/vllm/config/vllm.py
index 56123542ce71..394c9ca9fd0b 100644
--- a/vllm/config/vllm.py
+++ b/vllm/config/vllm.py
@@ -709,6 +709,48 @@ def _post_init_kv_transfer_config(self) -> None:
         # This is the same for all backends
         self.kv_transfer_config.kv_role = "kv_both"
 
+    def _verify_kv_transfer_compat(self) -> None:
+        """Reject configurations that silently corrupt KV transfers."""
+        if (
+            self.kv_transfer_config is None
+            or self.kv_transfer_config.kv_connector is None
+        ):
+            return
+
+        # PyTorch's expandable_segments allocator uses CUDA VMM, which can
+        # remap a virtual address range to different physical pages over the
+        # engine's lifetime. KV connectors that pin KV cache memory (e.g.
+        # NixlConnector via ibv_reg_mr, MooncakeConnector) end up with their
+        # registrations pointing at stale physical pages after any remap,
+        # producing RDMA failures like IBV_WC_REM_ACCESS_ERR /
+        # NIXL_ERR_REMOTE_DISCONNECT at the first inter-node KV transfer.
+        # We can't enumerate every in-tree and out-of-tree connector that
+        # pins memory, so we conservatively reject the combination whenever
+        # any KV connector is configured.
+        #
+        # Sleep mode is exempt: CuMemAllocator.use_memory_pool toggles
+        # expandable_segments off around its pool (see #40812), so the KV
+        # cache allocated within that context lands on stable physical pages
+        # even when the env var is set.
+        if "expandable_segments:True" not in os.environ.get(
+            "PYTORCH_CUDA_ALLOC_CONF", ""
+        ):
+            return
+        if self.model_config is not None and self.model_config.enable_sleep_mode:
+            return
+
+        raise ValueError(
+            f"KV connector {self.kv_transfer_config.kv_connector} is "
+            "incompatible with PYTORCH_CUDA_ALLOC_CONF=expandable_segments:True "
+            "unless enable_sleep_mode is also enabled. PyTorch's CUDA VMM "
+            "allocator can remap KV cache virtual addresses to different "
+            "physical pages, invalidating any pinned/registered KV memory "
+            "(e.g. IB memory regions registered by NIXL or Mooncake). Either "
+            "unset expandable_segments:True or enable sleep mode (which "
+            "routes KV allocations through CuMemAllocator's pool, where "
+            "expandable_segments is automatically disabled)."
+        )
+
     def __post_init__(self):
         """Verify configs are valid & consistent with each other."""
 
@@ -1343,6 +1385,7 @@ def has_blocked_weights():
 
         # Handle the KV connector configs
         self._post_init_kv_transfer_config()
+        self._verify_kv_transfer_compat()
 
         # Log the custom passes that are enabled
         self.compilation_config.pass_config.log_enabled_passes()