diff --git a/packages/react-native/Libraries/Core/InitializeCore.js b/packages/react-native/Libraries/Core/InitializeCore.js
index fdbbb50634b..f01d96e0df1 100644
--- a/packages/react-native/Libraries/Core/InitializeCore.js
+++ b/packages/react-native/Libraries/Core/InitializeCore.js
@@ -29,7 +29,7 @@
 const start = Date.now();
 
 require('./setUpGlobals');
-require('../../src/private/setup/setUpDOM');
+require('../../src/private/setup/setUpDOM').default();
 require('./setUpPerformance');
 require('./setUpErrorHandling');
 require('./polyfillPromise');
diff --git a/packages/react-native/src/private/setup/setUpDOM.js b/packages/react-native/src/private/setup/setUpDOM.js
index 0a75bd8dab8..04f12e49dd6 100644
--- a/packages/react-native/src/private/setup/setUpDOM.js
+++ b/packages/react-native/src/private/setup/setUpDOM.js
@@ -11,8 +11,18 @@
 import DOMRect from '../webapis/dom/geometry/DOMRect';
 import DOMRectReadOnly from '../webapis/dom/geometry/DOMRectReadOnly';
 
-// $FlowExpectedError[cannot-write] The global isn't writable anywhere but here, where we define it
-global.DOMRect = DOMRect;
+let initialized = false;
 
-// $FlowExpectedError[cannot-write] The global isn't writable anywhere but here, where we define it
-global.DOMRectReadOnly = DOMRectReadOnly;
+export default function setUpDOM() {
+  if (initialized) {
+    return;
+  }
+
+  initialized = true;
+
+  // $FlowExpectedError[cannot-write] The global isn't writable anywhere but here, where we define it
+  global.DOMRect = DOMRect;
+
+  // $FlowExpectedError[cannot-write] The global isn't writable anywhere but here, where we define it
+  global.DOMRectReadOnly = DOMRectReadOnly;
+}
diff --git a/packages/react-native/src/private/setup/setUpIntersectionObserver.js b/packages/react-native/src/private/setup/setUpIntersectionObserver.js
index 026f6415641..773a6d9f6d8 100644
--- a/packages/react-native/src/private/setup/setUpIntersectionObserver.js
+++ b/packages/react-native/src/private/setup/setUpIntersectionObserver.js
@@ -10,7 +10,18 @@
 
 import {polyfillGlobal} from '../../../Libraries/Utilities/PolyfillFunctions';
 
-polyfillGlobal(
-  'IntersectionObserver',
-  () => require('../webapis/intersectionobserver/IntersectionObserver').default,
-);
+let initialized = false;
+
+export default function setUpIntersectionObserver() {
+  if (initialized) {
+    return;
+  }
+
+  initialized = true;
+
+  polyfillGlobal(
+    'IntersectionObserver',
+    () =>
+      require('../webapis/intersectionobserver/IntersectionObserver').default,
+  );
+}
diff --git a/packages/react-native/src/private/setup/setUpMutationObserver.js b/packages/react-native/src/private/setup/setUpMutationObserver.js
index 00e1b7fd7fd..387d893ab75 100644
--- a/packages/react-native/src/private/setup/setUpMutationObserver.js
+++ b/packages/react-native/src/private/setup/setUpMutationObserver.js
@@ -10,7 +10,17 @@
 
 import {polyfillGlobal} from '../../../Libraries/Utilities/PolyfillFunctions';
 
-polyfillGlobal(
-  'MutationObserver',
-  () => require('../webapis/mutationobserver/MutationObserver').default,
-);
+let initialized = false;
+
+export default function setUpMutationObserver() {
+  if (initialized) {
+    return;
+  }
+
+  initialized = true;
+
+  polyfillGlobal(
+    'MutationObserver',
+    () => require('../webapis/mutationobserver/MutationObserver').default,
+  );
+}
diff --git a/packages/react-native/src/private/setup/setUpPerformanceObserver.js b/packages/react-native/src/private/setup/setUpPerformanceObserver.js
index e4b03cf3bb4..4f304741f89 100644
--- a/packages/react-native/src/private/setup/setUpPerformanceObserver.js
+++ b/packages/react-native/src/private/setup/setUpPerformanceObserver.js
@@ -10,44 +10,54 @@
 
 import {polyfillGlobal} from '../../../Libraries/Utilities/PolyfillFunctions';
 
-polyfillGlobal(
-  'PerformanceObserver',
-  () => require('../webapis/performance/PerformanceObserver').default,
-);
+let initialized = false;
 
-polyfillGlobal(
-  'PerformanceObserverEntryList',
-  () =>
-    require('../webapis/performance/PerformanceObserver')
-      .PerformanceObserverEntryList,
-);
+export default function setUpPerformanceObserver() {
+  if (initialized) {
+    return;
+  }
 
-polyfillGlobal(
-  'PerformanceEntry',
-  () => require('../webapis/performance/PerformanceEntry').PerformanceEntry,
-);
+  initialized = true;
 
-polyfillGlobal(
-  'PerformanceMark',
-  () => require('../webapis/performance/UserTiming').PerformanceMark,
-);
+  polyfillGlobal(
+    'PerformanceObserver',
+    () => require('../webapis/performance/PerformanceObserver').default,
+  );
 
-polyfillGlobal(
-  'PerformanceMeasure',
-  () => require('../webapis/performance/UserTiming').PerformanceMeasure,
-);
+  polyfillGlobal(
+    'PerformanceObserverEntryList',
+    () =>
+      require('../webapis/performance/PerformanceObserver')
+        .PerformanceObserverEntryList,
+  );
 
-polyfillGlobal(
-  'PerformanceEventTiming',
-  () => require('../webapis/performance/EventTiming').PerformanceEventTiming,
-);
+  polyfillGlobal(
+    'PerformanceEntry',
+    () => require('../webapis/performance/PerformanceEntry').PerformanceEntry,
+  );
 
-polyfillGlobal(
-  'TaskAttributionTiming',
-  () => require('../webapis/performance/LongTasks').TaskAttributionTiming,
-);
+  polyfillGlobal(
+    'PerformanceMark',
+    () => require('../webapis/performance/UserTiming').PerformanceMark,
+  );
 
-polyfillGlobal(
-  'PerformanceLongTaskTiming',
-  () => require('../webapis/performance/LongTasks').PerformanceLongTaskTiming,
-);
+  polyfillGlobal(
+    'PerformanceMeasure',
+    () => require('../webapis/performance/UserTiming').PerformanceMeasure,
+  );
+
+  polyfillGlobal(
+    'PerformanceEventTiming',
+    () => require('../webapis/performance/EventTiming').PerformanceEventTiming,
+  );
+
+  polyfillGlobal(
+    'TaskAttributionTiming',
+    () => require('../webapis/performance/LongTasks').TaskAttributionTiming,
+  );
+
+  polyfillGlobal(
+    'PerformanceLongTaskTiming',
+    () => require('../webapis/performance/LongTasks').PerformanceLongTaskTiming,
+  );
+}