diff --git a/packages/components/CHANGELOG.md b/packages/components/CHANGELOG.md
index 8cb09113d05bcf..58d5275fd750d5 100644
--- a/packages/components/CHANGELOG.md
+++ b/packages/components/CHANGELOG.md
@@ -9,6 +9,7 @@
 ### Bug Fix
 
 -   `Autocomplete`: Fix unexpected block insertion during IME composition ([#45510](https://github.com/WordPress/gutenberg/pull/45510)).
+-   `ToolsPanelItem`: Prevent unintended calls to onDeselect when parent panel is remounted and item is rendered via SlotFill ([#45673](https://github.com/WordPress/gutenberg/pull/45673))
 
 ### Internal
 
diff --git a/packages/components/src/tools-panel/tools-panel-item/hook.ts b/packages/components/src/tools-panel/tools-panel-item/hook.ts
index 582ff88113dba5..4e0db5b9881d3e 100644
--- a/packages/components/src/tools-panel/tools-panel-item/hook.ts
+++ b/packages/components/src/tools-panel/tools-panel-item/hook.ts
@@ -108,11 +108,15 @@ export function useToolsPanelItem(
 	const menuGroup = isShownByDefault ? 'default' : 'optional';
 	const isMenuItemChecked = menuItems?.[ menuGroup ]?.[ label ];
 	const wasMenuItemChecked = usePrevious( isMenuItemChecked );
+	const isRegistered = menuItems?.[ menuGroup ]?.[ label ] !== undefined;
 
 	// Determine if the panel item's corresponding menu is being toggled and
 	// trigger appropriate callback if it is.
 	useEffect( () => {
-		if ( isResetting || ! hasMatchingPanel ) {
+		// We check whether this item is currently registered as items rendered
+		// via fills can persist through the parent panel being remounted.
+		// See: https://github.com/WordPress/gutenberg/pull/45673
+		if ( ! isRegistered || isResetting || ! hasMatchingPanel ) {
 			return;
 		}