The United captain picked up an injury during the club's draw with Leicester City last weekend.
Louis van Gaal has confirmed that Manchester United will be without Wayne Rooney for their upcoming Premier League game with West Ham United, while it is also expected that he will miss their Champions League clash with Wolfsburg next week, The Telegraph report.
The Red Devils skipper injured his ankle during United's draw with Leicester City, and the Dutchman confirmed that the problem is worse than initially feared.
"He shall not play his 500th game because he is more injured than I thought. So we have to wait for that game. His ankle is not good enough and he has to recover that ankle with a lot of strength," he said.
Although Rooney has struggled for form this season - with only two goals to his name in the league - the news of his absence is a major blow to the Red Devils.
Saturday's game against Slaven Bilic's side presents United with the opportunity to potentially go to the top of the table. However, should the Hammers claim all three points, and other results conspire against them, they could fall out of the top four.
It would be an even bigger blow to United if Rooney missed their pivotal clash with the Bundesliga outfit next Tuesday. Failure to beat Dieter Hecking's men could allow PSV Eindhoven the opportunity to take United's place in the knockout phase of the competition.