"Wayne's is heavier than we thought- when we go on it's been getting worse so we have to let him train to make the ankle stronger" said manager Louis van Gaal.
"I cannot say how long he will be out for but he shall not play in the match against West Ham or against Wolfsburg" confirmed the Dutchman.
Marcos Rojo (dislocated shoulder), Ander Herrera (ankle) and Phil Jones (groin) will all miss out whilst Luke Shaw and Antonio Valencia are long term absentees.
With Rojo and Shaw both injured- leaving the Reds short of options at left-back- van Gaal was asked whether he will continue with the three at the back deployed at Leicester last time out.
"It is dependable on the opponent and also on the shape of my players so I have to compare." added the boss in his media conference on Friday.
"I know the coach of West Ham a little bit- I have seen how he works with his teams and he plays always more or less from the defensive organisation so they shall be difficult to beat I think.
"He always has them well organised in a good shape and they have proved that already because I have seen that they have won more games away from home and against some of the top teams also so it shall be not so easy again."
Slaven Bilic's Hammers made a blistering start to their season and have won at Anfield, the Emirates and Anfield so far this term, at one stage sitting as high as second in the table ahead of their move to the Olympic Stadium in Stratford next term.
They have gone off the boil in recent weeks though and have not picked up a win in the league since the 24th October when they saw off champions Chelsea at Upton Park and come to Old Trafford in eighth position.
Injuries to string-puller in chief Dimitri Payet and powerhouse strikers Diafra Sakho and Enner Valencia have not aided their cause, but Andy Carroll looks set to start and his height and aerial ability will pose an equally stiff challenge for United's well-drilled defence.
Form guide: United D W W W D D West Ham W W L D L D
Match odds: United 12/25 Draw 18/5 West Ham 36/5
Referee: Mark Clattenburg