diff --git a/.changelog/4718.changed b/.changelog/4718.changed
new file mode 100644
index 0000000000..190c17a7d2
--- /dev/null
+++ b/.changelog/4718.changed
@@ -0,0 +1 @@
+opentelemetry-instrumentation-urllib3: remove multiple calls to sanitize_method
\ No newline at end of file
diff --git a/instrumentation/opentelemetry-instrumentation-urllib3/benchmark-requirements.txt b/instrumentation/opentelemetry-instrumentation-urllib3/benchmark-requirements.txt
new file mode 100644
index 0000000000..5ddc9d46f4
--- /dev/null
+++ b/instrumentation/opentelemetry-instrumentation-urllib3/benchmark-requirements.txt
@@ -0,0 +1,5 @@
+mocket==3.14.1
+pytest-benchmark==4.0.0
+-e opentelemetry-instrumentation
+-e util/opentelemetry-util-http
+-e instrumentation/opentelemetry-instrumentation-urllib3
diff --git a/instrumentation/opentelemetry-instrumentation-urllib3/benchmarks/test_benchmark_sanitize_method.py b/instrumentation/opentelemetry-instrumentation-urllib3/benchmarks/test_benchmark_sanitize_method.py
new file mode 100644
index 0000000000..e320e3aa84
--- /dev/null
+++ b/instrumentation/opentelemetry-instrumentation-urllib3/benchmarks/test_benchmark_sanitize_method.py
@@ -0,0 +1,43 @@
+# Copyright The OpenTelemetry Authors
+# SPDX-License-Identifier: Apache-2.0
+
+import pytest
+import urllib3
+from mocket import Mocketizer
+from mocket.mocks.mockhttp import Entry
+
+from opentelemetry.instrumentation.urllib3 import URLLib3Instrumentor
+from opentelemetry.sdk.trace import TracerProvider
+from opentelemetry.sdk.trace.export import SimpleSpanProcessor
+from opentelemetry.sdk.trace.export.in_memory_span_exporter import (
+    InMemorySpanExporter,
+)
+
+_URL = "http://mock/status/200"
+
+
+@pytest.fixture(name="connection_pool")
+def _connection_pool_fixture():
+    exporter = InMemorySpanExporter()
+    provider = TracerProvider()
+    provider.add_span_processor(SimpleSpanProcessor(exporter))
+    URLLib3Instrumentor().instrument(tracer_provider=provider)
+    pool = urllib3.HTTPConnectionPool("mock", port=80)
+    with Mocketizer():
+        Entry.single_register(
+            Entry.GET, _URL, body="Hello!", match_querystring=False
+        )
+        yield pool
+    URLLib3Instrumentor().uninstrument()
+
+
+def test_instrumented_urlopen(
+    benchmark, connection_pool: urllib3.HTTPConnectionPool
+):
+    def run():
+        Entry.single_register(
+            Entry.GET, _URL, body="Hello!", match_querystring=False
+        )
+        connection_pool.urlopen("GET", "/status/200")
+
+    benchmark(run)
diff --git a/instrumentation/opentelemetry-instrumentation-urllib3/src/opentelemetry/instrumentation/urllib3/__init__.py b/instrumentation/opentelemetry-instrumentation-urllib3/src/opentelemetry/instrumentation/urllib3/__init__.py
index ab5660cc74..4728c09ba6 100644
--- a/instrumentation/opentelemetry-instrumentation-urllib3/src/opentelemetry/instrumentation/urllib3/__init__.py
+++ b/instrumentation/opentelemetry-instrumentation-urllib3/src/opentelemetry/instrumentation/urllib3/__init__.py
@@ -406,11 +406,10 @@ def _uninstrument(self, **kwargs):
         _uninstrument()
 
 
-def _get_span_name(method: str) -> str:
-    method = sanitize_method(method.strip())
-    if method == "_OTHER":
-        method = "HTTP"
-    return method
+def _get_span_name(sanitized_method: str) -> str:
+    if sanitized_method == "_OTHER":
+        return "HTTP"
+    return sanitized_method
 
 
 # pylint: disable=too-many-locals,too-many-positional-arguments
@@ -457,13 +456,14 @@ def instrumented_urlopen(wrapped, instance, args, kwargs):
         # avoid modifying original headers on inject
         headers = headers.copy() if headers is not None else {}
 
-        span_name = _get_span_name(method)
+        sanitized_method = sanitize_method(method)
+        span_name = _get_span_name(sanitized_method)
         span_attributes = {}
 
         _set_http_method(
             span_attributes,
             method,
-            sanitize_method(method),
+            sanitized_method,
             sem_conv_opt_in_mode,
         )
         _set_http_url(span_attributes, url, sem_conv_opt_in_mode)
@@ -519,6 +519,7 @@ def instrumented_urlopen(wrapped, instance, args, kwargs):
                 instance,
                 response,
                 method,
+                sanitized_method,
                 sem_conv_opt_in_mode,
             )
 
@@ -625,6 +626,7 @@ def _set_metric_attributes(
     instance: urllib3.connectionpool.HTTPConnectionPool,
     response: urllib3.response.HTTPResponse,
     method: str,
+    sanitized_method: str,
     sem_conv_opt_in_mode: _StabilityMode = _StabilityMode.DEFAULT,
 ) -> None:
     _set_http_host_client(
@@ -634,7 +636,7 @@ def _set_metric_attributes(
     _set_http_method(
         metric_attributes,
         method,
-        sanitize_method(method),
+        sanitized_method,
         sem_conv_opt_in_mode,
     )
     _set_http_net_peer_name_client(
diff --git a/tox.ini b/tox.ini
index f8315f4650..b59c469210 100644
--- a/tox.ini
+++ b/tox.ini
@@ -202,6 +202,7 @@ envlist =
     pypy3-test-instrumentation-logging
     lint-instrumentation-logging
     benchmark-instrumentation-logging
+    benchmark-instrumentation-urllib3
 
     ; opentelemetry-exporter-richconsole
     py3{10,11,12,13,14}-test-exporter-richconsole
@@ -691,6 +692,7 @@ deps =
   logging: {[testenv]test_deps}
   logging: -r {toxinidir}/instrumentation/opentelemetry-instrumentation-logging/test-requirements.txt
   benchmark-instrumentation-logging: -r {toxinidir}/instrumentation/opentelemetry-instrumentation-logging/benchmark-requirements.txt
+  benchmark-instrumentation-urllib3: -r {toxinidir}/instrumentation/opentelemetry-instrumentation-urllib3/benchmark-requirements.txt
 
   aiohttp-client: {[testenv]test_deps}
   aiohttp-client: -r {toxinidir}/instrumentation/opentelemetry-instrumentation-aiohttp-client/test-requirements.txt
@@ -893,6 +895,7 @@ commands =
   test-instrumentation-logging: pytest {toxinidir}/instrumentation/opentelemetry-instrumentation-logging/tests {posargs}
   lint-instrumentation-logging: sh -c "cd instrumentation && pylint --rcfile ../.pylintrc opentelemetry-instrumentation-logging"
   benchmark-instrumentation-logging: pytest {toxinidir}/instrumentation/opentelemetry-instrumentation-logging/benchmarks {posargs} --benchmark-json=instrumentation-logging-benchmark.json
+  benchmark-instrumentation-urllib3: pytest {toxinidir}/instrumentation/opentelemetry-instrumentation-urllib3/benchmarks {posargs} --benchmark-json=instrumentation-urllib3-benchmark.json
 
   test-instrumentation-mysql: pytest {toxinidir}/instrumentation/opentelemetry-instrumentation-mysql/tests {posargs}
   lint-instrumentation-mysql: sh -c "cd instrumentation && pylint --rcfile ../.pylintrc opentelemetry-instrumentation-mysql"