Manchester United defenders John O'Shea and Jonny Evans have both been ruled out of action until January.
Evans has been struggling with a calf injury while O'Shea's problem was not specified by the club.
The double blow is part of an atrocious injury situation which leaves Sir Alex Ferguson without 12 players, including Nemanja Vidic, for Tuesday night's game against Wolfsburg.
Vidic has been ruled out with flu, leaving Ferguson with a threadbare defence as his team attempt to secure top spot in Group B.
Owen Hargreaves, who is still troubled by a knee complaint which has kept him out all season, will also miss the midweek fixture.
United ended Saturday's 4-0 win at West Ham with Michael Carrick and Patrice Evra in the centre of defence, Ryan Giggs at left-back and Darren Fletcher at right-back. And Ferguson confirmed Wayne Rooney and Dimitar Berbatov took minor knocks at West Ham.
Rooney has hamstring injury while Berbatov has a knee problem, with both rated doubtful for Saturday's home game with Aston Villa. But it is in central defence where Ferguson has the biggest headache.
It appears he is trying to persuade Evra to face Wolfsburg's impressive forward duo Edin Dzeko and Grafite alongside Carrick, who has already been confirmed as a centre-half. Another option would be Darren Fletcher, with Park-Ji Sung occupying a full-back berth.
Ferguson had hoped there would be an improvement in the situation by the weekend but while Nemanja Vidic should have recovered from flu, the outlook for Wes Brown, who limped off at Upton Park with a hamstring injury, is not as positive.
"We are hoping to have to Wes fit but hamstring injuries are difficult. It is not an easy one," said Ferguson.
Copyright (c) PA Sport 2009, All Rights Reserved.