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 today.
It is more bad news on the defensive front for manager Sir Alex Ferguson, who 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.
The double blow is part of an atrocious injury situation which leaves Ferguson without 12 players for tomorrow night's game, plus the rested Giggs and Owen Hargreaves, who is still troubled by a knee complaint which has kept him out all season.
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.