Robin van Persie is set to miss the Manchester derby after Louis van Gaal said he is unlikely to be fit enough to return by next weekend.
Netherlands' record scorer will sit out a sixth consecutive Manchester United game when Aston Villa visit Old Trafford on Saturday.
And though he is back in training and could feature for United's under-21s against West Ham on Tuesday, Van Gaal believes he will not be ready for the meeting with Manchester City.
"I don't think so," the manager said in a news conference. "He's still not [training] in my group [with the first-team squad]. The process has to give me signals he is ready for that. But I know that from my experience it is not like that. And everybody is fit."
Van Gaal has used previous Under-21 games to give players a chance to recapture match sharpness and could do so again with Van Persie.
"That is possible, like the others," he added.
United have produced arguably their two best performances of the season in their last two games, when Van Persie has been absent and when record signing Angel Di Maria was suspended for the 3-0 win over Tottenham. But Van Gaal insisted he had not found a winning formula by accident after two of his regulars were ruled out.
"You can say that and therefore you can think it's accidentally but I don't think so," he said.
Van Gaal may have to make one alteration to his side against Villa, as defender Chris Smalling is ill, but explained why he will always consider making changes.
"There is an expression that you never change a winning team," he added. "It's an English expression I believe, and that's true. But I'm always analysing the data what I can receive, also the quality of the opponent and then I make a decision, not only with me but with my staff, on the line-up."
While Van Gaal is adamant he has not given up hope of winning the title, second place is a more realistic target, making the City game pivotal.
"I cannot deny that because we have Manchester City at home," he said. "We have the strongest record at home at home so it's possible. But Manchester City is a top team so it shall not be easy."
United have been criticised for their performances by some of their ex-players this season, but former captain Gary Neville has praised them for their displays in recent games.
Van Gaal was pleased, but revealed it would mean more to him if Sir Alex Ferguson hailed his side.
"It's nice for the players, and also nice for the manager when legends are saying that," he said. "I think that if for example Ferguson when he says that then I am more proud because he can judge as a manager much better than ex-players what is the achievement in such a game."
Van Gaal was asked if he had spoken to Ferguson recently and replied: "He is always on his way so it's difficult to speak with him. But we have made an appointment and he shall pay -- that is very important!"