diff --git a/experimental/CHANGELOG.md b/experimental/CHANGELOG.md
index f0fb0ed5ea9..67f3f771dde 100644
--- a/experimental/CHANGELOG.md
+++ b/experimental/CHANGELOG.md
@@ -21,6 +21,7 @@ All notable changes to experimental packages in this project will be documented
   * allows for experimental usage of this instrumentation with non-browser runtimes
 * fix(instrumentation-http): memory leak when responses are not resumed
 * fix(instrumentation-fetch): compatibility with Map types for fetch headers
+* fix(instrumentation-http): Do not mutate given headers object for outgoing http requests. Fixes aws-sdk signing error on retries. [#4346](https://github.com/open-telemetry/opentelemetry-js/pull/4346)
 
 ## 0.45.1
 
diff --git a/experimental/packages/opentelemetry-instrumentation-http/src/http.ts b/experimental/packages/opentelemetry-instrumentation-http/src/http.ts
index 81e08ac860b..337d058033d 100644
--- a/experimental/packages/opentelemetry-instrumentation-http/src/http.ts
+++ b/experimental/packages/opentelemetry-instrumentation-http/src/http.ts
@@ -675,6 +675,10 @@ export class HttpInstrumentation extends InstrumentationBase<Http> {
 
       if (!optionsParsed.headers) {
         optionsParsed.headers = {};
+      } else {
+        // Make a copy of the headers object to avoid mutating an object the
+        // caller might have a reference to.
+        optionsParsed.headers = Object.assign({}, optionsParsed.headers);
       }
       propagation.inject(requestContext, optionsParsed.headers);
 
diff --git a/experimental/packages/opentelemetry-instrumentation-http/test/integrations/http-enable.test.ts b/experimental/packages/opentelemetry-instrumentation-http/test/integrations/http-enable.test.ts
index 625b8b65499..a04027a2c95 100644
--- a/experimental/packages/opentelemetry-instrumentation-http/test/integrations/http-enable.test.ts
+++ b/experimental/packages/opentelemetry-instrumentation-http/test/integrations/http-enable.test.ts
@@ -269,6 +269,20 @@ describe('HttpInstrumentation Integration tests', () => {
       assertSpan(span, SpanKind.CLIENT, validations);
     });
 
+    it('should not mutate given headers object when adding propagation headers', async () => {
+      const spans = memoryExporter.getFinishedSpans();
+      assert.strictEqual(spans.length, 0);
+
+      const headers = { 'x-foo': 'foo' };
+      const result = await httpRequest.get(
+        new url.URL(`${protocol}://localhost:${mockServerPort}/?query=test`),
+        { headers }
+      );
+      assert.deepStrictEqual(headers, { 'x-foo': 'foo' });
+      assert.ok(result.reqHeaders[DummyPropagation.TRACE_CONTEXT_KEY]);
+      assert.ok(result.reqHeaders[DummyPropagation.SPAN_CONTEXT_KEY]);
+    });
+
     it('should create a span for GET requests and add propagation headers with Expect headers', async () => {
       let spans = memoryExporter.getFinishedSpans();
       assert.strictEqual(spans.length, 0);