Germany international Mustafi has been struggling with a knock while midfielder Xhaka faces a race against time to be fit due to a groin problem.
Arsenal boss Arsene Wenger will continue his touchline ban as the Gunners look set to return to a full-strength side following their 4-2 FA Cup defeat at Nottingham Forest over the weekend.
Having taken plenty of criticism for their performance at the City Ground, Wenger is looking for a response from his side at Stamford Bridge on Wednesday night.
“We take the criticism on board and respond to it in a positive way – that’s all you can do,” he said. “We’re in the semi-final of the League Cup and we have an opportunity to go through.”