diff --git a/instrumentation-genai/opentelemetry-instrumentation-langchain/CHANGELOG.md b/instrumentation-genai/opentelemetry-instrumentation-langchain/CHANGELOG.md
index c3d51f9fef..3c1c9beb97 100644
--- a/instrumentation-genai/opentelemetry-instrumentation-langchain/CHANGELOG.md
+++ b/instrumentation-genai/opentelemetry-instrumentation-langchain/CHANGELOG.md
@@ -8,4 +8,6 @@ and this project adheres to [Semantic Versioning](https://semver.org/spec/v2.0.0
 ## Unreleased
 
 - Added span support for genAI langchain llm invocation.
-  ([#3665](https://github.com/open-telemetry/opentelemetry-python-contrib/pull/3665))
\ No newline at end of file
+  ([#3665](https://github.com/open-telemetry/opentelemetry-python-contrib/pull/3665))
+- Use weak reference in langchain instrumentation span map.
+  ([#3735](https://github.com/open-telemetry/opentelemetry-python-contrib/pull/3735))
\ No newline at end of file
diff --git a/instrumentation-genai/opentelemetry-instrumentation-langchain/pyproject.toml b/instrumentation-genai/opentelemetry-instrumentation-langchain/pyproject.toml
index 4f3e88115b..c1f217b68a 100644
--- a/instrumentation-genai/opentelemetry-instrumentation-langchain/pyproject.toml
+++ b/instrumentation-genai/opentelemetry-instrumentation-langchain/pyproject.toml
@@ -27,7 +27,8 @@ classifiers = [
 dependencies = [
   "opentelemetry-api >= 1.31.0",
   "opentelemetry-instrumentation ~= 0.57b0",
-  "opentelemetry-semantic-conventions ~= 0.57b0"
+  "opentelemetry-semantic-conventions ~= 0.57b0",
+  "cachetools >= 5.2.0",
 ]
 
 [project.optional-dependencies]
diff --git a/instrumentation-genai/opentelemetry-instrumentation-langchain/src/opentelemetry/instrumentation/langchain/span_manager.py b/instrumentation-genai/opentelemetry-instrumentation-langchain/src/opentelemetry/instrumentation/langchain/span_manager.py
index 636bfc3bc3..f02f828f3b 100644
--- a/instrumentation-genai/opentelemetry-instrumentation-langchain/src/opentelemetry/instrumentation/langchain/span_manager.py
+++ b/instrumentation-genai/opentelemetry-instrumentation-langchain/src/opentelemetry/instrumentation/langchain/span_manager.py
@@ -13,9 +13,11 @@
 # limitations under the License.
 
 from dataclasses import dataclass, field
+from threading import RLock
 from typing import Dict, List, Optional
 from uuid import UUID
 
+from cachetools import TTLCache
 from opentelemetry.semconv._incubating.attributes import (
     gen_ai_attributes as GenAI,
 )
@@ -40,10 +42,11 @@ def __init__(
         tracer: Tracer,
     ) -> None:
         self._tracer = tracer
+        self._lock = RLock()
 
         # Map from run_id -> _SpanState, to keep track of spans and parent/child relationships
-        # TODO: Use weak references or a TTL cache to avoid memory leaks in long-running processes. See #3735
-        self.spans: Dict[UUID, _SpanState] = {}
+        # Using a TTL cache to avoid memory leaks in long-running processes where end_span might not be called.
+        self.spans: TTLCache[UUID, _SpanState] = TTLCache(maxsize=1024, ttl=3600)
 
     def _create_span(
         self,
@@ -52,23 +55,24 @@ def _create_span(
         span_name: str,
         kind: SpanKind = SpanKind.INTERNAL,
     ) -> Span:
-        if parent_run_id is not None and parent_run_id in self.spans:
-            parent_state = self.spans[parent_run_id]
-            parent_span = parent_state.span
-            ctx = set_span_in_context(parent_span)
-            span = self._tracer.start_span(
-                name=span_name, kind=kind, context=ctx
-            )
-            parent_state.children.append(run_id)
-        else:
-            # top-level or missing parent
-            span = self._tracer.start_span(name=span_name, kind=kind)
-            set_span_in_context(span)
-
-        span_state = _SpanState(span=span)
-        self.spans[run_id] = span_state
-
-        return span
+        with self._lock:
+            if parent_run_id is not None and parent_run_id in self.spans:
+                parent_state = self.spans[parent_run_id]
+                parent_span = parent_state.span
+                ctx = set_span_in_context(parent_span)
+                span = self._tracer.start_span(
+                    name=span_name, kind=kind, context=ctx
+                )
+                parent_state.children.append(run_id)
+            else:
+                # top-level or missing parent
+                span = self._tracer.start_span(name=span_name, kind=kind)
+                set_span_in_context(span)
+
+            span_state = _SpanState(span=span)
+            self.spans[run_id] = span_state
+
+            return span
 
     def create_chat_span(
         self,
@@ -92,18 +96,25 @@ def create_chat_span(
         return span
 
     def end_span(self, run_id: UUID) -> None:
-        state = self.spans[run_id]
-        for child_id in state.children:
-            child_state = self.spans.get(child_id)
-            if child_state:
-                child_state.span.end()
-                del self.spans[child_id]
-        state.span.end()
-        del self.spans[run_id]
+        with self._lock:
+            state = self.spans.get(run_id)
+            if not state:
+                return
+            # End children first (make a copy to avoid modification during iteration)
+            for child_id in list(state.children):
+                child_state = self.spans.get(child_id)
+                if child_state:
+                    child_state.span.end()
+                    # Use pop to avoid KeyError if already expired
+                    self.spans.pop(child_id, None)
+            state.span.end()
+            # Use pop to avoid KeyError if already expired
+            self.spans.pop(run_id, None)
 
     def get_span(self, run_id: UUID) -> Optional[Span]:
-        state = self.spans.get(run_id)
-        return state.span if state else None
+        with self._lock:
+            state = self.spans.get(run_id)
+            return state.span if state else None
 
     def handle_error(self, error: BaseException, run_id: UUID):
         span = self.get_span(run_id)
diff --git a/instrumentation-genai/opentelemetry-instrumentation-langchain/tests/test_span_manager.py b/instrumentation-genai/opentelemetry-instrumentation-langchain/tests/test_span_manager.py
index 69de5a7146..131e0409e6 100644
--- a/instrumentation-genai/opentelemetry-instrumentation-langchain/tests/test_span_manager.py
+++ b/instrumentation-genai/opentelemetry-instrumentation-langchain/tests/test_span_manager.py
@@ -1,5 +1,6 @@
 import unittest.mock
 import uuid
+import time
 
 import pytest
 
@@ -98,3 +99,24 @@ def test_end_span(self, handler):
         child_mock_span.end.assert_called_once()
         assert run_id not in handler.spans
         assert child_run_id not in handler.spans
+
+    def test_ttl_cache_expires_spans(self, tracer):
+        # Arrange - Create handler with short TTL
+        from cachetools import TTLCache
+        
+        handler = _SpanManager(tracer=tracer)
+        # Replace the cache with one that has a very short TTL
+        handler.spans = TTLCache(maxsize=1024, ttl=0.05)
+        
+        run_id = uuid.uuid4()
+        mock_span = unittest.mock.Mock(spec=Span)
+        handler.spans[run_id] = _SpanState(span=mock_span)
+
+        # Assert - Span exists immediately
+        assert run_id in handler.spans
+
+        # Act - Wait for TTL to expire
+        time.sleep(0.1)
+
+        # Assert - Span is automatically removed by TTL
+        assert run_id not in handler.spans