diff --git a/CHANGELOG.md b/CHANGELOG.md
index 74105aa672..eb4f59e119 100644
--- a/CHANGELOG.md
+++ b/CHANGELOG.md
@@ -8,6 +8,8 @@ and this project adheres to [Semantic Versioning](https://semver.org/spec/v2.0.0
 ## [Unreleased](https://github.com/open-telemetry/opentelemetry-python/compare/v1.12.0rc1-0.31b0...HEAD)
 
 ### Fixed
+- Adding escape call to fix [auto-instrumentation not producing spans on Windows](https://github.com/open-telemetry/opentelemetry-python/issues/2703).
+  ([#1100](https://github.com/open-telemetry/opentelemetry-python-contrib/pull/1100))
 - `opentelemetry-instrumentation-grpc` narrow protobuf dependency to exclude protobuf >= 4
   ([1109](https://github.com/open-telemetry/opentelemetry-python-contrib/pull/1109))
 - cleanup type hints for textmap `Getter` and `Setter` classes
diff --git a/opentelemetry-instrumentation/src/opentelemetry/instrumentation/auto_instrumentation/sitecustomize.py b/opentelemetry-instrumentation/src/opentelemetry/instrumentation/auto_instrumentation/sitecustomize.py
index 25ee3fe048..9504e359af 100644
--- a/opentelemetry-instrumentation/src/opentelemetry/instrumentation/auto_instrumentation/sitecustomize.py
+++ b/opentelemetry-instrumentation/src/opentelemetry/instrumentation/auto_instrumentation/sitecustomize.py
@@ -15,7 +15,6 @@
 from logging import getLogger
 from os import environ
 from os.path import abspath, dirname, pathsep
-from re import sub
 
 from pkg_resources import iter_entry_points
 
@@ -26,6 +25,7 @@
 from opentelemetry.instrumentation.environment_variables import (
     OTEL_PYTHON_DISABLED_INSTRUMENTATIONS,
 )
+from opentelemetry.instrumentation.utils import _python_path_without_directory
 from opentelemetry.instrumentation.version import __version__
 
 logger = getLogger(__name__)
@@ -111,10 +111,8 @@ def _load_configurators():
 
 def initialize():
     # prevents auto-instrumentation of subprocesses if code execs another python process
-    environ["PYTHONPATH"] = sub(
-        rf"{dirname(abspath(__file__))}{pathsep}?",
-        "",
-        environ["PYTHONPATH"],
+    environ["PYTHONPATH"] = _python_path_without_directory(
+        environ["PYTHONPATH"], dirname(abspath(__file__)), pathsep
     )
 
     try:
diff --git a/opentelemetry-instrumentation/src/opentelemetry/instrumentation/utils.py b/opentelemetry-instrumentation/src/opentelemetry/instrumentation/utils.py
index 56f174d758..fea7608388 100644
--- a/opentelemetry-instrumentation/src/opentelemetry/instrumentation/utils.py
+++ b/opentelemetry-instrumentation/src/opentelemetry/instrumentation/utils.py
@@ -13,6 +13,7 @@
 # limitations under the License.
 
 import urllib.parse
+from re import escape, sub
 from typing import Dict, Sequence
 
 from wrapt import ObjectProxy
@@ -163,3 +164,11 @@ def _generate_opentelemetry_traceparent(span: Span) -> str:
     _traceparent = _version + "-" + _trace_id + "-" + _span_id + "-" + _flags
     meta.update({"traceparent": _traceparent})
     return meta
+
+
+def _python_path_without_directory(python_path, directory, path_separator):
+    return sub(
+        rf"{escape(directory)}{path_separator}(?!$)",
+        "",
+        python_path,
+    )
diff --git a/opentelemetry-instrumentation/tests/test_utils.py b/opentelemetry-instrumentation/tests/test_utils.py
index ac8b9268c3..b7c9ecdc6e 100644
--- a/opentelemetry-instrumentation/tests/test_utils.py
+++ b/opentelemetry-instrumentation/tests/test_utils.py
@@ -14,7 +14,10 @@
 
 from http import HTTPStatus
 
-from opentelemetry.instrumentation.utils import http_status_to_status_code
+from opentelemetry.instrumentation.utils import (
+    _python_path_without_directory,
+    http_status_to_status_code,
+)
 from opentelemetry.test.test_base import TestBase
 from opentelemetry.trace import StatusCode
 
@@ -111,3 +114,41 @@ def test_http_status_to_status_code_server(self):
                     int(status_code), server_span=True
                 )
                 self.assertEqual(actual, expected, status_code)
+
+    def test_remove_current_directory_from_python_path_windows(self):
+        directory = r"c:\users\Trayvon Martin\workplace\opentelemetry-python-contrib\opentelemetry-instrumentation\src\opentelemetry\instrumentation\auto_instrumentation"
+        path_separator = r";"
+        python_path = r"c:\users\Trayvon Martin\workplace\opentelemetry-python-contrib\opentelemetry-instrumentation\src\opentelemetry\instrumentation\auto_instrumentation;C:\Users\trayvonmartin\workplace"
+        actual_python_path = _python_path_without_directory(
+            python_path, directory, path_separator
+        )
+        expected_python_path = r"C:\Users\trayvonmartin\workplace"
+        self.assertEqual(actual_python_path, expected_python_path)
+
+    def test_remove_current_directory_from_python_path_linux(self):
+        directory = r"/home/georgefloyd/workplace/opentelemetry-python-contrib/opentelemetry-instrumentation/src/opentelemetry/instrumentation/auto_instrumentation"
+        path_separator = r":"
+        python_path = r"/home/georgefloyd/workplace/opentelemetry-python-contrib/opentelemetry-instrumentation/src/opentelemetry/instrumentation/auto_instrumentation:/home/georgefloyd/workplace"
+        actual_python_path = _python_path_without_directory(
+            python_path, directory, path_separator
+        )
+        expected_python_path = r"/home/georgefloyd/workplace"
+        self.assertEqual(actual_python_path, expected_python_path)
+
+    def test_remove_current_directory_from_python_path_windows_only_path(self):
+        directory = r"c:\users\Charleena Lyles\workplace\opentelemetry-python-contrib\opentelemetry-instrumentation\src\opentelemetry\instrumentation\auto_instrumentation"
+        path_separator = r";"
+        python_path = r"c:\users\Charleena Lyles\workplace\opentelemetry-python-contrib\opentelemetry-instrumentation\src\opentelemetry\instrumentation\auto_instrumentation"
+        actual_python_path = _python_path_without_directory(
+            python_path, directory, path_separator
+        )
+        self.assertEqual(actual_python_path, python_path)
+
+    def test_remove_current_directory_from_python_path_linux_only_path(self):
+        directory = r"/home/SandraBland/workplace/opentelemetry-python-contrib/opentelemetry-instrumentation/src/opentelemetry/instrumentation/auto_instrumentation"
+        path_separator = r":"
+        python_path = r"/home/SandraBland/workplace/opentelemetry-python-contrib/opentelemetry-instrumentation/src/opentelemetry/instrumentation/auto_instrumentation"
+        actual_python_path = _python_path_without_directory(
+            python_path, directory, path_separator
+        )
+        self.assertEqual(actual_python_path, python_path)