Manchester United forward Angel di Maria has failed to recover from a hamstring injury in time to face rivals Liverpool on Sunday.
The Argentina international has missed United's past two Premier League fixtures with Stoke City and Southampton, but there was hope he could recover in time to face Brendan Rodgers' men at Old Trafford.
However, manager Louis van Gaal has confirmed that the 26-year-old will once more have to sit out as United seek a sixth straight victory.
Centre-back Chris Smalling is also set to miss two weeks of action with a groin injury sustained in Monday's 2-1 win at Southampton.
Full-back Luke Shaw and midfielder Daley Blind remain United's other absentees, but defensive duo Phil Jones (shin) and Rafael (muscle) are set to come back into contention.
Striker Radamel Falcao is also set to be involved in some capacity and Van Gaal is optimistic that United's injury issues are finally relenting.
"Now I only have four players injured," he said at his pre-match news conference. "So that's better than ever.
"Only Shaw, Smalling, Di Maria and Blind [are injured]. He [Falcao] could make a return."
United have climbed to third as a result of their five-match winning streak and Van Gaal paid tribute to his team for getting results despite having several key players absent.
"We have managed our last five matches," he continued. "I'm very pleased with that, in spite of our list of injuries.
"That is very good I think. As a manager you have to give a lot of credit to the players because it's not so easy."