The England forward sat out of the 2-1 win over Reading in the fifth round of the FA Cup on Monday night due to a sinus problem. Despite reports the 27-year-old was likely to make his return against Harry Redknapp's men, the striker will remain sidelined after failing to train for most of the week.
Sir Alex Ferguson will also be without defender Phil Jones, who was injured during the win over Reading, with Ferguson saying that all the focus is on getting Jones fit for the second leg of United's UEFA Champions League round of 16 tie with Real Madrid.
"Phil Jones is the one we are really concerned about in terms of the Real Madrid game,” Ferguson told reporters. “We're working hard on it and I'd say he has an outside chance – no more than that. He won't be fit for the weekend."
The Premier League leader goes into the game 12 points ahead of closest competitor and current champions Manchester City, while the Rs are rooted to the bottom of the table, seven points behind 17th-place Aston Villa, which is languishing just outside the relegation zone.
The game poses a good opportunity for United to further extend its lead, with three points against the bottom boys meaning Roberto Mancini's men would be 15 points behind when they play Chelsea on Sunday.
Meanwhile, a win for Redknapp's side would provide a huge boost in their push for survival, particularly with many of the bottoms sides facing each other at the weekend. The two clubs immediately above the Hoops, Reading and Wigan, face each other at the Madejski Stadium on Saturday, while 16th-placed Newcastle hosts 15th-placed Southampton on Sunday.
Follow GOAL.COM on Twitter