United manager Alex Ferguson, who marked his 23rd anniversary in charge of the club on Friday, said that experts have been unable to pinpoint the nature of a calf injury which has sidelined the defender for the last two weeks.
"We don't know exactly where the calf injury is coming from," Ferguson told a news conference. "Whether it is coming from the lower back, whether it is a nerve thing.
"But calf injuries are normally two to three weeks and he is showing no sign of recovering from that injury. We're looking at the whole situation, whether it is coming from the back or not, but in the meantime he is out. There is no improvement so obviously we are looking at something different."
Ferdinand, who turns 31 on Saturday, has had his form widely questioned after indifferent performances for United and Fabio Capello's England team so far this season and the potential for an extended spell on the sidelines constitutes a major setback.
Serbian defender Nemanja Vidic has been passed fit for the clash with Chelsea, along with midfielder Darren Fletcher who has recovered from a minor injury collected in the midweek Champions League draw against CSKA Moscow.
Ferguson, 67, would like nothing more than to mark his anniversary at Old Trafford with a rare victory at Stamford Bridge, his club having failed to win there in the last seven visits. Chelsea top the standings on 27 points from 11 matches, two ahead of second-placed United.
The Scot is clearly relishing the challenge of what is viewed by many as a possible title decider, despite his longevity in the job.
"I don't think so," said Ferguson when asked whether his desire is lessening with the years. "Whether other people judge it differently, I don't know.
"But in the main, I have been lucky. I have had my health and that's all you can be thankful for. As you get older, there are different deteriorations in health, maybe small things, you can't avoid it. But, as I say, I have been lucky.
"Chelsea is a big game and, hopefully, we can improve our record down there because it has not been good the last six years or so. I think the players realise it is a big game and their performance is going to be important."
