Louis van Gaal has confirmed that he will be without Luke Shaw, Ander Herrera, Chris Smalling and Marcos Rojo for the Manchester United's Boxing Day clash against Newcastle.
Marouane Fellaini is also out of the game while Daley Blind is a long-term absentee.
With the games now coming thick and fast over the Christmas period Van Gaal will need to use his full squad so the fact that he will be without a host of first teams stars will be a major blow.
It had been claimed that Shaw should be back in action for the game at Old Trafford on Friday, but it appears as though it has come too soon. Smalling is the only one who stands a chance of taking part, but even that isn't guaranteed.
"For a few players it is fine because they recover very quickly." he said. "But you also have players you are not recovering so quickly so I am having to rotate."But my problem is that I have a lot of injured players. That is the problem of these matches in the coming weeks. Smalling maybe (can come back). I have to look. But that's like always."
Although Blind is nowhere near full fitness for the game, he has returned to training as he steps up his rehabilitation from a knee injury. Rojo is close to a return too, but won't be back in time to face Newcastle.
One man who is fit and firing for Manchester United is Radamel Falcao. The Colombian forward was on the scoresheet for the Red Devils in their 1-1 draw with Aston Villa at the weekend, and is in line for more game time over Christmas.
The strike against Paul Lambert's side was just his second of the season following a calf injury, and Van Gaal believes the former Porto ace can now start to deliver on his promise.
The Dutch boss said: "I'm very pleased he scored a beautiful goal [vs Villa] & I hope he'll follow it with a lot of other goals."
The draw against Paul Lambert's side marked the end of a six-game winning run which has taken them up to third in the Premier League heading into the new year.