diff --git a/packages/grafana-runtime/src/utils/DataSourceWithBackend.test.ts b/packages/grafana-runtime/src/utils/DataSourceWithBackend.test.ts
index 7c996cea7c5..db7a43baa03 100644
--- a/packages/grafana-runtime/src/utils/DataSourceWithBackend.test.ts
+++ b/packages/grafana-runtime/src/utils/DataSourceWithBackend.test.ts
@@ -42,7 +42,8 @@ jest.mock('../services', () => ({
 
 describe('DataSourceWithBackend', () => {
   test('check the executed queries', () => {
-    const mock = runQueryAndReturnFetchMock({
+    const { mock, ds } = createMockDatasource();
+    ds.query({
       maxDataPoints: 10,
       intervalMs: 5000,
       targets: [{ refId: 'A' }, { refId: 'B', datasource: { type: 'sample' } }],
@@ -93,8 +94,22 @@ describe('DataSourceWithBackend', () => {
     `);
   });
 
+  test('should apply template variables only for the current data source', () => {
+    const { mock, ds } = createMockDatasource();
+    ds.applyTemplateVariables = jest.fn();
+    ds.query({
+      maxDataPoints: 10,
+      intervalMs: 5000,
+      targets: [{ refId: 'A' }, { refId: 'B', datasource: { type: 'sample' } }],
+    } as DataQueryRequest);
+
+    expect(mock.calls.length).toBe(1);
+    expect(ds.applyTemplateVariables).toHaveBeenCalledTimes(1);
+  });
+
   test('check that the executed queries is hidden from inspector', () => {
-    const mock = runQueryAndReturnFetchMock({
+    const { mock, ds } = createMockDatasource();
+    ds.query({
       maxDataPoints: 10,
       intervalMs: 5000,
       targets: [{ refId: 'A' }, { refId: 'B', datasource: { type: 'sample' } }],
@@ -169,9 +184,7 @@ describe('DataSourceWithBackend', () => {
   });
 });
 
-function runQueryAndReturnFetchMock(
-  request: DataQueryRequest
-): jest.MockContext<Promise<FetchResponse>, BackendSrvRequest[]> {
+function createMockDatasource() {
   const settings = {
     name: 'test',
     id: 1234,
@@ -184,7 +197,5 @@ function runQueryAndReturnFetchMock(
   mockDatasourceRequest.mockReturnValue(Promise.resolve({} as FetchResponse));
 
   const ds = new MyDataSource(settings);
-  ds.query(request);
-
-  return mockDatasourceRequest.mock;
+  return { ds, mock: mockDatasourceRequest.mock };
 }
diff --git a/packages/grafana-runtime/src/utils/DataSourceWithBackend.ts b/packages/grafana-runtime/src/utils/DataSourceWithBackend.ts
index 9cdc73b7d72..15c2bd947e3 100644
--- a/packages/grafana-runtime/src/utils/DataSourceWithBackend.ts
+++ b/packages/grafana-runtime/src/utils/DataSourceWithBackend.ts
@@ -133,6 +133,7 @@ class DataSourceWithBackend<
     const queries = targets.map((q) => {
       let datasource = this.getRef();
       let datasourceId = this.id;
+      let shouldApplyTemplateVariables = true;
 
       if (isExpressionReference(q.datasource)) {
         hasExpr = true;
@@ -149,8 +150,15 @@ class DataSourceWithBackend<
           throw new Error(`Unknown Datasource: ${JSON.stringify(q.datasource)}`);
         }
 
-        datasource = ds.rawRef ?? getDataSourceRef(ds);
-        datasourceId = ds.id;
+        const dsRef = ds.rawRef ?? getDataSourceRef(ds);
+        const dsId = ds.id;
+        if (dsRef.uid !== datasource.uid || datasourceId !== dsId) {
+          datasource = dsRef;
+          datasourceId = dsId;
+          // If the query is using a different datasource, we would need to retrieve the datasource
+          // instance (async) and apply the template variables but it seems it's not necessary for now.
+          shouldApplyTemplateVariables = false;
+        }
       }
       if (datasource.type?.length) {
         pluginIDs.add(datasource.type);
@@ -159,7 +167,7 @@ class DataSourceWithBackend<
         dsUIDs.add(datasource.uid);
       }
       return {
-        ...this.applyTemplateVariables(q, request.scopedVars),
+        ...(shouldApplyTemplateVariables ? this.applyTemplateVariables(q, request.scopedVars) : q),
         datasource,
         datasourceId, // deprecated!
         intervalMs,