Sir Alex Ferguson has ruled defensive duo Gary Neville and Wes Brown out of the Premier League clash with Fulham - and virtually dashed any hope Anderson had of making next week's Carling Cup Final.
Neville is still recovering from a virus, while Brown has not yet reached full fitness, despite a couple of substitute appearances after an ankle operation.
Neither man will be considered for the Cottagers clash, as United look to stretch their lead at the top of the table to five points.
Meanwhile Anderson, who would almost certainly have been involved against Tottenham at Wembley on Sunday week, is still some weeks away from a return to action after suffering an ankle injury in the latter stages of the semi-final win over Derby.
But with Wayne Rooney back after a hamstring injury, Ferguson has plenty of options on Wednesday for a game originally postponed last August due to United's European Super Cup commitments.
"If we win the gap is five points, which is a fantastic incentive for us," Ferguson told MUTV.
"It would allow us to look at the league in its proper perspective."
United are looking for a 14th consecutive top flight clean sheet, a run that has continued uninterrupted despite their successful Club World Cup campaign in Japan before Christmas.
Even Ferguson now concedes he was concerned about the impact it would have on his side's domestic season. But, once they had returned to England and won at Stoke on Boxing Day, the Scot had no fears for United's future.
"We didn't know whether Japan was a hurdle we could overcome," said Ferguson.
"Even I had my doubts. But winning that match at Stoke on Boxing Day kick-started our season."
Although, in theory, Aston Villa and Chelsea remain challengers, in reality only Liverpool would be in a position to stop the Red Devils claiming an 18th title, allowing them to move level with the Anfield outfit.
But for record signing Dimitar Berbatov, such historical milestones pale into insignificance alongside his desperate desire to land a first Premier League crown.
"The players here who have already won it, need it again and again and again," he said.
"I have none of that. When I am here, it is like I need it - I want it.
"With the help of everybody, with the right amount of effort on the pitch and with the team we have, I am pretty sure we can win it again."
