Manchester United are waiting to see how long captain Wayne Rooney will be out for after his ankle problem ensured he will not face West Ham, with the striker also a major doubt for the club's crucial Champions League game against Wolfsburg next week.
United defender Marcos Rojo is out with a dislocated shoulder, giving manager Louis van Gaal defensive injury problems.
Rooney, who has made 499 appearances for United, came off with a knock in last week's 1-1 draw with Leicester and will not feature at Old Trafford on Saturday.
"It's more heavy than we thought and a nasty injury," Van Gaal told MUTV. "When we go on it's been getting worse. We have to let him train to make the ankle stronger, that's very important. I cannot say [how long he's out for] because the doctor shall decide that with Wayne of course. He is training well in the rehabilitation."
When asked if Rooney would miss the match at Wolfsburg, Van Gaal said: "Yes, I think so."
United must win at Wolfsburg on Tuesday to guarantee their place in the knockout phase of the Champions League. If United draw with the German side, they will be eliminated if PSV Eindhoven beat CSKA Moscow in the other Group B match. If United lose to Wolfsburg, they will be eliminated if PSV get a point against CSKA.
Argentina international Rojo, who was out for four weeks with a dislocated shoulder last year, was injured in training on Wednesday, exacerbating United's left-back shortage.
First-choice Luke Shaw has been ruled out for at least six months with the broken leg he sustained in United's September defeat to PSV Eindhoven.
"Rojo has been injured," Van Gaal added. "It's his shoulder, the same as last year, in a training session. It's very unfortunate, also in the position of Luke Shaw so I have a great problem."
Van Gaal could select either Daley Blind or youngster Cameron Borthwick-Jackson on the left of his defence but could need to choose his fellow Dutchman at centre-back as Phil Jones is still injured.
The defender, who has an ankle problem, remains out after missing United's last two matches while midfielder Ander Herrera, who suffered a hamstring injury in the 2-1 win at Watford and has sat out the same games, is also still sidelined.
It means Van Gaal is short of four frontline defenders, with right-back Antonio Valencia, who had foot surgery, another long-term absentee.
But he will at least be able to welcome back Jesse Lingard, who missed the draw with Leicester with a minor hamstring injury.