diff --git a/packages/react-aria-components/test/ComboBox.browser.test.tsx b/packages/react-aria-components/test/ComboBox.browser.test.tsx
index 9eeae701923..60f3f7e1adf 100644
--- a/packages/react-aria-components/test/ComboBox.browser.test.tsx
+++ b/packages/react-aria-components/test/ComboBox.browser.test.tsx
@@ -26,7 +26,10 @@ import {Label} from '../src/Label';
 import {ListBox, ListBoxItem} from '../src/ListBox';
 import {Popover} from '../src/Popover';
 import React from 'react';
+import {UNSAFE_PortalProvider} from 'react-aria/PortalProvider';
 import {User} from '@react-aria/test-utils';
+import userEvent from '@testing-library/user-event';
+import {within} from '@testing-library/dom';
 
 function TestComboBox() {
   return (
@@ -119,4 +122,74 @@ describe('Shadow DOM', () => {
     root.unmount();
     document.body.removeChild(outerHost);
   });
+
+  it.each`
+    interactionType
+    ${'mouse'}
+    ${'keyboard'}
+  `('selects an option via $interactionType', async ({interactionType}) => {
+    const host = document.createElement('div');
+    const shadowRoot = host.attachShadow({mode: 'open'});
+    const appContainer = document.createElement('div');
+    shadowRoot.appendChild(appContainer);
+    document.body.appendChild(host);
+    const portalHost = document.createElement('div');
+    const shadowPortal = portalHost.attachShadow({mode: 'open'});
+    const portalContainer = document.createElement('div');
+    shadowPortal.appendChild(portalContainer);
+    const button = document.createElement('button');
+    shadowPortal.appendChild(button);
+    document.body.appendChild(portalHost);
+    const root = createRoot(appContainer);
+
+    root.render(
+      <UNSAFE_PortalProvider getContainer={() => portalContainer}>
+        <TestComboBox />
+      </UNSAFE_PortalProvider>
+    );
+
+    await new Promise(resolve => setTimeout(resolve, 100));
+    const trigger = shadowRoot.querySelector('button')!;
+    await open();
+    const listbox = getListbox();
+    expect(listbox).not.toBeNull();
+
+    if (interactionType === 'keyboard') {
+      await userEvent.keyboard('{ArrowDown}');
+      await userEvent.keyboard('[Enter]');
+    } else if (interactionType === 'mouse') {
+      const option = within(listbox!).queryAllByRole('option')[1];
+      await userEvent.click(option);
+    }
+
+    await new Promise(resolve => setTimeout(resolve, 100));
+    expect(getListbox()).toBeNull();
+    expect(getCombobox()).toHaveValue('Dog');
+    await open();
+    expect(getListbox()).not.toBeNull();
+    await userEvent.click(button);
+    expect(getListbox()).toBeNull();
+    root.unmount();
+    document.body.removeChild(host);
+    document.body.removeChild(portalHost);
+
+    async function open() {
+      if (interactionType === 'mouse') {
+        await userEvent.click(trigger);
+      } else if (interactionType === 'keyboard') {
+        // oxlint-disable-next-line rsp-rules/act-events-test
+        getCombobox()?.focus();
+        await userEvent.keyboard('{ArrowDown}');
+      }
+    }
+
+    function getCombobox() {
+      return shadowRoot.querySelector<HTMLElement>('[role="combobox"]');
+    }
+
+    function getListbox() {
+      const listBoxId = getCombobox()?.getAttribute('aria-controls');
+      return listBoxId ? shadowPortal.getElementById(listBoxId) || null : null;
+    }
+  });
 });
diff --git a/packages/react-aria/src/combobox/useComboBox.ts b/packages/react-aria/src/combobox/useComboBox.ts
index e8d688e8104..9d9dc6f7b96 100644
--- a/packages/react-aria/src/combobox/useComboBox.ts
+++ b/packages/react-aria/src/combobox/useComboBox.ts
@@ -28,7 +28,7 @@ import {
 import {AriaListBoxOptions} from '../listbox/useListBox';
 import {chain} from '../utils/chain';
 import {ComboBoxProps, ComboBoxState, SelectionMode} from 'react-stately/useComboBoxState';
-import {dispatchVirtualFocus} from '../focus/virtualFocus';
+import {dispatchVirtualFocus, getOriginalRelatedTarget} from '../focus/virtualFocus';
 import {
   ElementType,
   FocusEvent,
@@ -268,7 +268,10 @@ export function useComboBox<T, M extends SelectionMode = 'single'>(
 
   let onBlur = (e: FocusEvent<HTMLInputElement>) => {
     let blurFromButton = nodeContains(buttonRef.current, e.relatedTarget as Element);
-    let blurIntoPopover = nodeContains(popoverRef.current, e.relatedTarget);
+    let blurIntoPopover = nodeContains(
+      popoverRef.current,
+      getOriginalRelatedTarget(e.nativeEvent) as Element
+    );
 
     // Ignore blur if focused moved to the button(if exists) or into the popover.
     if (blurFromButton || blurIntoPopover) {
diff --git a/packages/react-aria/src/focus/virtualFocus.ts b/packages/react-aria/src/focus/virtualFocus.ts
index a50248a1f82..6bf79880845 100644
--- a/packages/react-aria/src/focus/virtualFocus.ts
+++ b/packages/react-aria/src/focus/virtualFocus.ts
@@ -1,5 +1,6 @@
 import {getActiveElement} from '../utils/shadowdom/DOMFunctions';
 import {getOwnerDocument} from '../utils/domHelpers';
+import {shadowDOM} from 'react-stately/private/flags/flags';
 
 export function moveVirtualFocus(to: Element | null): void {
   let from = getVirtuallyFocusedElement(getOwnerDocument(to));
@@ -14,13 +15,13 @@ export function moveVirtualFocus(to: Element | null): void {
 }
 
 export function dispatchVirtualBlur(from: Element, to: Element | null): void {
-  from.dispatchEvent(new FocusEvent('blur', {relatedTarget: to}));
-  from.dispatchEvent(new FocusEvent('focusout', {bubbles: true, relatedTarget: to}));
+  from.dispatchEvent(createFocusEvent('blur', {relatedTarget: to}));
+  from.dispatchEvent(createFocusEvent('focusout', {bubbles: true, relatedTarget: to}));
 }
 
 export function dispatchVirtualFocus(to: Element, from: Element | null): void {
-  to.dispatchEvent(new FocusEvent('focus', {relatedTarget: from}));
-  to.dispatchEvent(new FocusEvent('focusin', {bubbles: true, relatedTarget: from}));
+  to.dispatchEvent(createFocusEvent('focus', {relatedTarget: from}));
+  to.dispatchEvent(createFocusEvent('focusin', {bubbles: true, relatedTarget: from}));
 }
 
 export function getVirtuallyFocusedElement(document: Document): Element | null {
@@ -32,3 +33,23 @@ export function getVirtuallyFocusedElement(document: Document): Element | null {
 
   return activeElement;
 }
+
+let originalRelatedTargetMap: WeakMap<FocusEvent, EventTarget> | null = null;
+function createFocusEvent(type: string, eventInitDict?: FocusEventInit) {
+  const event = new FocusEvent(type, eventInitDict);
+  if (shadowDOM()) {
+    originalRelatedTargetMap ??= new WeakMap();
+    const relatedTarget = event.relatedTarget;
+    if (relatedTarget !== null) {
+      originalRelatedTargetMap.set(event, relatedTarget);
+    }
+  }
+  return event;
+}
+
+export function getOriginalRelatedTarget(event: FocusEvent): EventTarget | null {
+  if (!shadowDOM()) {
+    return event.relatedTarget;
+  }
+  return originalRelatedTargetMap?.get(event) ?? event.relatedTarget;
+}