Jose Mourinho has confirmed Chris Smalling and Phil Jones are out with "long-term injuries", but Wayne Rooney is in line to face West Brom on Saturday.
Smalling pulled out of the England squad after playing in a friendly defeat to Germany, while Jones sustained a toe problem after a challenge from his team-mate in training with his country.
Rooney has not played since the start of March with a knee injury but could feature against the Baggies at Old Trafford this weekend, when Paul Pogba (hamstring) will miss out.
Despite injuries and suspensions - Zlatan Ibrahimovic and Ander Herrera are banned - stacking up, Mourinho emphasised the need to focus on those who he can call upon.
Speaking about Smalling and Jones, the United manager said: "They are long-term injuries.
"The important ones are the ones who are ready to play. That's the way we have to think, we cannot be here crying or speaking about the players that are not available to play.
"You know about Zlatan and Herrera, they are suspended. You know that Herrera has two matches banned for that episode against Chelsea. You know what happened in the English national team with Smalling and Jones. You know that we have also Pogba injured.
"But I repeat they're not important. The important players are the ones that are ready to play, and the ones I trust, and the ones who are going to give everything to try to keep us in the fight for the top four."
United have not lost in the Premier League since October and sit fifth, with two games and four points to make up on fourth-placed Liverpool.