diff --git a/metapackages/auto-instrumentations-node/README.md b/metapackages/auto-instrumentations-node/README.md
index 0c71574801..2674dfd4fe 100644
--- a/metapackages/auto-instrumentations-node/README.md
+++ b/metapackages/auto-instrumentations-node/README.md
@@ -97,6 +97,9 @@ To disable only [@opentelemetry/instrumentation-fs](https://github.com/open-tele
 export OTEL_NODE_DISABLED_INSTRUMENTATIONS="fs"
 ```
 
+If both environment variables are set, `OTEL_NODE_ENABLED_INSTRUMENTATIONS` is applied first, and then `OTEL_NODE_DISABLED_INSTRUMENTATIONS` is applied to that list.
+Therefore, if the same instrumentation is included in both lists, that instrumentation will be disabled.
+
 To enable logging for troubleshooting, set the log level by setting the `OTEL_LOG_LEVEL` environment variable to one of the following:
 
 - `none`
diff --git a/metapackages/auto-instrumentations-node/test/utils.test.ts b/metapackages/auto-instrumentations-node/test/utils.test.ts
index ceea3262a8..cc7cb24c68 100644
--- a/metapackages/auto-instrumentations-node/test/utils.test.ts
+++ b/metapackages/auto-instrumentations-node/test/utils.test.ts
@@ -114,6 +114,25 @@ describe('utils', () => {
       }
     });
 
+    it('should disable any instrumentations from OTEL_NODE_ENABLED_INSTRUMENTATIONS if set in OTEL_NODE_DISABLED_INSTRUMENTATIONS', () => {
+      process.env.OTEL_NODE_ENABLED_INSTRUMENTATIONS = 'http,express,net';
+      process.env.OTEL_NODE_DISABLED_INSTRUMENTATIONS = 'fs,net'; // fs is no-op here, already disabled
+      try {
+        const instrumentations = getNodeAutoInstrumentations();
+
+        assert.deepStrictEqual(
+          new Set(instrumentations.map(i => i.instrumentationName)),
+          new Set([
+            '@opentelemetry/instrumentation-http',
+            '@opentelemetry/instrumentation-express',
+          ])
+        );
+      } finally {
+        delete process.env.OTEL_NODE_DISABLED_INSTRUMENTATIONS;
+        delete process.env.OTEL_NODE_ENABLED_INSTRUMENTATIONS;
+      }
+    });
+
     it('should show error for none existing instrumentation', () => {
       const spy = sinon.stub(diag, 'error');
       const name = '@opentelemetry/instrumentation-http2';