David Moyes' slim hopes of Champions League glory receded even further on Friday when Robin van Persie was ruled out for between four and six weeks with a knee injury.
Van Persie fired United into the last eight of the competition with a stunning hat-trick against Olympiacos on Wednesday, but he left the field on a stretcher following a tackle from behind in the dying minutes.
Moyes hoped the injury was not serious, but a second scan revealed the striker would be out for a considerable time.
A club official said: "Following further investigation Robin van Persie has a sprained knee, which will keep him out for around four to six weeks."
The worst-case scenario for Van Persie is that he is only able to play the final three league games of the season.
If Van Persie's rehabilitation goes as well as possible, he should be fit for United's game at Everton on April 20.
He will definitely be out of Saturday's trip to West Ham, the derby against Manchester City on Tuesday and both legs of United's Champions League quarter-final against reigning champions Bayern Munich.
Speaking before the length of Van Persie's absence was confirmed, the United manager said: "Robin van Persie scored three goals in the Champions League. I don't know how you would want to be without a player of his ability and qualities."
The Dutch Football Association will be concerned by the news too, given that Van Persie may only return just over a week before the end of the season.
Coach Louis Van Gaal will have to decide whether to include the player in his provisional World Cup squad on May 13.
One crumb of comfort for United is that Danny Welbeck has played well recently so Moyes will be hoping the England international can prove to be an able deputy - starting with Saturday's trip to Upton Park
A bigger test awaits Moyes against Munich, who come to Old Trafford on April 1 for the first leg.
Pep Guardiola has had little trouble adapting to life in Germany following his year-long sabbatical after leaving his role as coach of Barcelona.
Bayern are unbeaten atop the Bundesliga and they wasted little effort brushing aside Arsenal in the last 16.
Moyes has watched Bayern on a few occasions this year though and he is convinced there are weaknesses in the German side he can exploit.
"They have proved they are the best by winning the World Club Championship but I've had a chance to see Munich a few times, I watched them at Arsenal and they are a good team," Moyes said.
"But I've got a few things that I would say that I've seen that I would try to work on and capitalise on."