Sir Alex Ferguson has confirmed that Rio Ferdinand, Nemanja Vidic, Ji-sung Park and Ryan Giggs will all miss Tuesday's Champions League clash between Manchester United and CSKA Moscow at Old Trafford.
In addition, Bulgaria international Dimitar Berbatov is a doubt while Wayne Rooney may miss out as his wife Coleen has been admitted to hospital ahead of the birth of their first child, which is already nine days overdue.
Rooney missed training on Monday morning and has said in the past that he would prefer to be at the birth of his child rather than playing for United.
Meanwhile, Darren Fletcher has recovered from the injury he picked up while on Scotland duty last month, with Ferguson confirming:"Darren was a substitute on Saturday and will play on Tuesday.
"I think most people recognise Fletcher as a big game player. We've been aware of that for quite a while. Now there's an acceptance among most people that he's a very important player for us.
"He's been missed in some key games recently so it will be good to have him back."
Park was able to train on Monday after a recent absence with fluid on his knee, but the South Korea international is not expected to return to action for another two weeks.