diff --git a/packages/auto-instrumentations-node/src/utils.ts b/packages/auto-instrumentations-node/src/utils.ts
index ce5e1d1941..cda71e00f9 100644
--- a/packages/auto-instrumentations-node/src/utils.ts
+++ b/packages/auto-instrumentations-node/src/utils.ts
@@ -152,6 +152,50 @@ export type InstrumentationConfigMap = {
   >;
 };
 
+function shouldDisableInstrumentation(
+  name: string,
+  userConfig: any,
+  enabledInstrumentationsFromEnv: string[],
+  disabledInstrumentationsFromEnv: string[]
+): boolean {
+  // Priority 1: Programmatic config
+  if (userConfig.enabled === false) {
+    diag.debug(
+      `Disabling instrumentation for ${name} - disabled by user config`
+    );
+    return true;
+  }
+
+  if (userConfig.enabled === true) {
+    diag.debug(
+      `Enabling instrumentation for ${name} - explicitly enabled by user config`
+    );
+    return false;
+  }
+
+  // Priority 2: Environment variables
+  if (disabledInstrumentationsFromEnv.includes(name)) {
+    diag.debug(`Disabling instrumentation for ${name} - disabled by env var`);
+    return true;
+  }
+
+  const isEnabledEnvSet = !!process.env.OTEL_NODE_ENABLED_INSTRUMENTATIONS;
+  if (isEnabledEnvSet && !enabledInstrumentationsFromEnv.includes(name)) {
+    diag.debug(
+      `Disabling instrumentation for ${name} - not in enabled env var list`
+    );
+    return true;
+  }
+
+  // Priority 3: Default exclusions
+  if (!isEnabledEnvSet && defaultExcludedInstrumentations.includes(name)) {
+    diag.debug(`Disabling instrumentation for ${name} - excluded by default`);
+    return true;
+  }
+
+  return false;
+}
+
 export function getNodeAutoInstrumentations(
   inputConfigs: InstrumentationConfigMap = {}
 ): Instrumentation[] {
@@ -168,12 +212,14 @@ export function getNodeAutoInstrumentations(
     // Defaults are defined by the instrumentation itself
     const userConfig: any = inputConfigs[name] ?? {};
 
-    if (
-      userConfig.enabled === false ||
-      !enabledInstrumentationsFromEnv.includes(name) ||
-      disabledInstrumentationsFromEnv.includes(name)
-    ) {
-      diag.debug(`Disabling instrumentation for ${name}`);
+    const shouldDisable = shouldDisableInstrumentation(
+      name,
+      userConfig,
+      enabledInstrumentationsFromEnv,
+      disabledInstrumentationsFromEnv
+    );
+
+    if (shouldDisable) {
       continue;
     }
 
diff --git a/packages/auto-instrumentations-node/test/utils.test.ts b/packages/auto-instrumentations-node/test/utils.test.ts
index 1241ca6cce..c83fc520c0 100644
--- a/packages/auto-instrumentations-node/test/utils.test.ts
+++ b/packages/auto-instrumentations-node/test/utils.test.ts
@@ -172,6 +172,92 @@ describe('utils', () => {
 
       spy.restore();
     });
+
+    it('should enable fs instrumentation when explicitly enabled and OTEL_NODE_ENABLED_INSTRUMENTATIONS is not set', () => {
+      const instrumentations = getNodeAutoInstrumentations({
+        '@opentelemetry/instrumentation-fs': {
+          enabled: true,
+        },
+      });
+      const fsInstrumentation = instrumentations.find(
+        instr =>
+          instr.instrumentationName === '@opentelemetry/instrumentation-fs'
+      );
+      assert.notStrictEqual(
+        fsInstrumentation,
+        undefined,
+        'fs instrumentation should be included when explicitly enabled in config and env var is not set'
+      );
+    });
+
+    it('should respect programmatic config over OTEL_NODE_ENABLED_INSTRUMENTATIONS - user config overrides env var', () => {
+      process.env.OTEL_NODE_ENABLED_INSTRUMENTATIONS = 'fs,http';
+      try {
+        const instrumentations = getNodeAutoInstrumentations({
+          '@opentelemetry/instrumentation-fs': {
+            enabled: false, // User explicitly disables - should override env var
+          },
+          '@opentelemetry/instrumentation-express': {
+            enabled: true, // User explicitly enables - should override env var
+          },
+        });
+
+        const fsInstrumentation = instrumentations.find(
+          instr =>
+            instr.instrumentationName === '@opentelemetry/instrumentation-fs'
+        );
+        const httpInstrumentation = instrumentations.find(
+          instr =>
+            instr.instrumentationName === '@opentelemetry/instrumentation-http'
+        );
+        const expressInstrumentation = instrumentations.find(
+          instr =>
+            instr.instrumentationName ===
+            '@opentelemetry/instrumentation-express'
+        );
+
+        assert.strictEqual(
+          fsInstrumentation,
+          undefined,
+          'fs should be disabled by user config despite env var'
+        );
+        assert.notStrictEqual(
+          httpInstrumentation,
+          undefined,
+          'http should be enabled by env var (no user override)'
+        );
+        assert.notStrictEqual(
+          expressInstrumentation,
+          undefined,
+          'express should be enabled by user config despite not being in env var list'
+        );
+      } finally {
+        delete process.env.OTEL_NODE_ENABLED_INSTRUMENTATIONS;
+      }
+    });
+
+    it('should respect programmatic config over OTEL_NODE_DISABLED_INSTRUMENTATIONS - user config overrides env var', () => {
+      process.env.OTEL_NODE_DISABLED_INSTRUMENTATIONS = 'http';
+      try {
+        const instrumentations = getNodeAutoInstrumentations({
+          '@opentelemetry/instrumentation-http': {
+            enabled: true, // User explicitly enables - should override env var
+          },
+        });
+        const httpInstrumentation = instrumentations.find(
+          instr =>
+            instr.instrumentationName === '@opentelemetry/instrumentation-http'
+        );
+
+        assert.notStrictEqual(
+          httpInstrumentation,
+          undefined,
+          'http instrumentation should be enabled by user config despite OTEL_NODE_DISABLED_INSTRUMENTATIONS'
+        );
+      } finally {
+        delete process.env.OTEL_NODE_DISABLED_INSTRUMENTATIONS;
+      }
+    });
   });
 
   describe('getResourceDetectorsFromEnv', () => {