Wayne Rooney will miss Manchester United's home game against West Ham on Saturday and their key Champions League tie at Wolfsburg with an ankle injury.
The forward, 30, did not complete the 1-1 draw at Leicester City last weekend and will have to wait to make his 500th appearance for the club.
Manager Louis van Gaal said the issue was worse than previously thought and a "nasty injury".
United must win at Wolfsburg to be sure of advancing in the Champions League.
Van Gaal, whose side completes their Group B games in Germany on Tuesday, said he did not know how long Rooney would be unavailable.
"It's been getting worse," he told MUTV. "We have to let him train to make the ankle stronger. He is training well in the rehabilitation."
Van Gaal also confirmed reports defender Marcos Rojo had dislocated a shoulder in training, adding: "The question as to whether he shall be operated is a question for the doctor and for Marcos."
Defender Phil Jones and midfielder Ander Herrera will also miss the visit of eighth-placed West Ham, although winger Jesse Lingard is expected to return after missing the game at Leicester.