diff --git a/packages/grafana-ui/src/components/Combobox/MultiCombobox.test.tsx b/packages/grafana-ui/src/components/Combobox/MultiCombobox.test.tsx
index f92371b6e3b..4d3c1e0abee 100644
--- a/packages/grafana-ui/src/components/Combobox/MultiCombobox.test.tsx
+++ b/packages/grafana-ui/src/components/Combobox/MultiCombobox.test.tsx
@@ -117,6 +117,39 @@ describe('MultiCombobox', () => {
     expect(onChange).toHaveBeenNthCalledWith(3, [{ label: 'C', value: third }]);
   });
 
+  it('should allow for options to be deselected', async () => {
+    // This test ensures that our fix for async options doesn't break sync options
+    const options = [
+      { label: 'A', value: 'a' },
+      { label: 'B', value: 'b' },
+      { label: 'C', value: 'c' },
+    ];
+    const onChange = jest.fn();
+
+    const ControlledMultiCombobox = (props: MultiComboboxProps<string>) => {
+      const [value, setValue] = React.useState<string[]>(['a']);
+      return (
+        <MultiCombobox
+          {...props}
+          value={value}
+          onChange={(val) => {
+            setValue(val.map((v) => v.value));
+            onChange(val);
+          }}
+        />
+      );
+    };
+
+    render(<ControlledMultiCombobox options={options} value={[]} onChange={onChange} />);
+    const input = screen.getByRole('combobox');
+    await user.click(input);
+
+    // Click on option A to deselect it (it should be selected initially)
+    await user.click(await screen.findByRole('option', { name: 'A' }));
+
+    expect(onChange).toHaveBeenCalledWith([]);
+  });
+
   it('should be able to render a value that is not in the options', async () => {
     const options = [
       { label: 'A', value: 'a' },
@@ -378,6 +411,76 @@ describe('MultiCombobox', () => {
       expect(asyncOptions).toHaveBeenCalledTimes(1);
       expect(asyncOptions).toHaveBeenCalledWith('abc');
     });
+
+    it('should allow deselecting items', async () => {
+      const asyncOptions = jest.fn(() => Promise.resolve(simpleAsyncOptions));
+      render(<MultiCombobox options={asyncOptions} value={['Option 1']} onChange={onChangeHandler} />);
+
+      const input = screen.getByRole('combobox');
+      await user.click(input);
+
+      // Debounce
+      await act(async () => jest.advanceTimersByTime(200));
+
+      // Click on Option 1 to deselect it (it should already be selected via value prop)
+      const item = await screen.findByRole('option', { name: 'Option 1' });
+      await user.click(item);
+
+      // Verify onChange was called to remove the item
+      expect(onChangeHandler).toHaveBeenCalledWith([]);
+    });
+
+    it('should allow deselecting items with async options using ComboboxOption value format', async () => {
+      // This test reproduces the bug where deselection doesn't work with async options
+      // when the value is passed as ComboboxOption objects
+      const asyncOptionsData = [
+        { label: 'Integration A', value: 'a' },
+        { label: 'Integration B', value: 'b' },
+        { label: 'Integration C', value: 'c' },
+      ];
+
+      const asyncOptions = jest.fn(() => Promise.resolve(asyncOptionsData));
+
+      // Use a controlled component to simulate the user's scenario
+      const ControlledComponent = () => {
+        const [selectedValue, setSelectedValue] = React.useState<Array<ComboboxOption<string>>>([
+          { label: 'Integration A', value: 'a' },
+        ]);
+
+        return (
+          <MultiCombobox
+            options={asyncOptions}
+            value={selectedValue}
+            onChange={(options) => {
+              onChangeHandler(options);
+              setSelectedValue(options);
+            }}
+          />
+        );
+      };
+
+      render(<ControlledComponent />);
+
+      const input = screen.getByRole('combobox');
+      await user.click(input);
+
+      // Wait for async options to load
+      await act(async () => jest.advanceTimersByTime(200));
+
+      // Integration A should be selected (shown as pill)
+      const pillRemoveButton = screen.getByRole('button', { name: 'Remove Integration A' });
+      expect(pillRemoveButton).toBeInTheDocument();
+
+      // Click on Integration A in the dropdown to deselect it
+      const item = await screen.findByRole('option', { name: 'Integration A' });
+      await user.click(item);
+
+      // Verify onChange was called to remove the item
+      expect(onChangeHandler).toHaveBeenCalledWith([]);
+
+      // The pill should be removed
+      expect(screen.queryByRole('button', { name: 'Remove Integration A' })).not.toBeInTheDocument();
+    });
   });
 });
 
diff --git a/packages/grafana-ui/src/components/Combobox/MultiCombobox.tsx b/packages/grafana-ui/src/components/Combobox/MultiCombobox.tsx
index bd9a65b705c..e6a3723191c 100644
--- a/packages/grafana-ui/src/components/Combobox/MultiCombobox.tsx
+++ b/packages/grafana-ui/src/components/Combobox/MultiCombobox.tsx
@@ -118,7 +118,7 @@ export const MultiCombobox = <T extends string | number>(props: MultiComboboxPro
             break;
         }
       },
-      stateReducer: (state, actionAndChanges) => {
+      stateReducer: (_state, actionAndChanges) => {
         const { changes } = actionAndChanges;
         return {
           ...changes,
@@ -220,7 +220,13 @@ export const MultiCombobox = <T extends string | number>(props: MultiComboboxPro
             }
             setSelectedItems(newSelectedItems);
           } else if (newSelectedItem && isOptionSelected(newSelectedItem)) {
-            removeSelectedItem(newSelectedItem);
+            // Find the actual selected item object that matches the clicked item by value
+            // This is necessary because the clicked item (from async options) may be a different
+            // object reference than the selected item, and useMultipleSelection uses object equality
+            const itemToRemove = selectedItems.find((item) => item.value === newSelectedItem.value);
+            if (itemToRemove) {
+              removeSelectedItem(itemToRemove);
+            }
           } else if (newSelectedItem) {
             addSelectedItem(newSelectedItem);
           }