diff --git a/CHANGELOG.md b/CHANGELOG.md
index 16f54fea2d..2c9bec4e9a 100644
--- a/CHANGELOG.md
+++ b/CHANGELOG.md
@@ -24,6 +24,8 @@ and this project adheres to [Semantic Versioning](https://semver.org/spec/v2.0.0
   ([#3419](https://github.com/open-telemetry/opentelemetry-python-contrib/pull/3419))
 - `opentelemetry-instrumentation` don't print duplicated conflict log error message
   ([#3432](https://github.com/open-telemetry/opentelemetry-python-contrib/pull/3432))
+- `opentelemetry-instrumentation-grpc` Check for None result in gRPC
+  ([#3380](https://github.com/open-telemetry/opentelemetry-python-contrib/pull/3381))
 
 ## Version 1.32.0/0.53b0 (2025-04-10)
 
diff --git a/instrumentation/opentelemetry-instrumentation-grpc/src/opentelemetry/instrumentation/grpc/_client.py b/instrumentation/opentelemetry-instrumentation-grpc/src/opentelemetry/instrumentation/grpc/_client.py
index e27c9e826f..adc713678c 100644
--- a/instrumentation/opentelemetry-instrumentation-grpc/src/opentelemetry/instrumentation/grpc/_client.py
+++ b/instrumentation/opentelemetry-instrumentation-grpc/src/opentelemetry/instrumentation/grpc/_client.py
@@ -165,7 +165,7 @@ def _intercept(self, request, metadata, client_info, invoker):
                 span.record_exception(exc)
                 raise exc
             finally:
-                if not result:
+                if result is None:
                     span.end()
         return self._trace_result(span, rpc_info, result)
 
diff --git a/instrumentation/opentelemetry-instrumentation-grpc/tests/test_client_interceptor.py b/instrumentation/opentelemetry-instrumentation-grpc/tests/test_client_interceptor.py
index 9fb922a615..5be0141c3b 100644
--- a/instrumentation/opentelemetry-instrumentation-grpc/tests/test_client_interceptor.py
+++ b/instrumentation/opentelemetry-instrumentation-grpc/tests/test_client_interceptor.py
@@ -13,6 +13,8 @@
 # limitations under the License.
 # pylint:disable=cyclic-import
 
+from unittest import mock
+
 import grpc
 
 import opentelemetry.instrumentation.grpc
@@ -26,6 +28,7 @@
 )
 from opentelemetry.instrumentation.utils import suppress_instrumentation
 from opentelemetry.propagate import get_global_textmap, set_global_textmap
+from opentelemetry.sdk.trace import Span as SdkSpan
 from opentelemetry.semconv.trace import SpanAttributes
 from opentelemetry.test.mock_textmap import MockTextMapPropagator
 from opentelemetry.test.test_base import TestBase
@@ -269,6 +272,32 @@ def test_error_stream_stream(self):
             trace.StatusCode.ERROR,
         )
 
+    def test_client_interceptor_falsy_response(
+        self,
+    ):
+        """ensure that client interceptor closes the span only once even if the response is falsy."""
+
+        with mock.patch.object(SdkSpan, "end") as span_end_mock:
+            tracer_provider, _exporter = self.create_tracer_provider()
+            tracer = tracer_provider.get_tracer(__name__)
+
+            interceptor = OpenTelemetryClientInterceptor(tracer)
+
+            def invoker(_request, _metadata):
+                return {}
+
+            request = Request(client_id=1, request_data="data")
+            interceptor.intercept_unary(
+                request,
+                {},
+                _UnaryClientInfo(
+                    full_method="/GRPCTestServer/SimpleMethod",
+                    timeout=None,
+                ),
+                invoker=invoker,
+            )
+            self.assertEqual(span_end_mock.call_count, 1)
+
     def test_client_interceptor_trace_context_propagation(
         self,
     ):  # pylint: disable=no-self-use