Rooney played in midfield over the Christmas period but his performances became increasingly ineffectual in the role.
An injury to Robin van Persie meant Rooney was moved back up front and he has gone on to flourish back in his favoured position.
“It is the worst scenario,” Van Gaal said.
“Marcos and Phil can both play left central defender and Jonny Evans is also suspended so I do not have many choices.
Man United seemed to have finally found a winning combination in terms of the balance in their team but the injuries will threaten to derail their momentum.
In Rooney’s absence, the returning van Persie or Radamel Falcao could start up front against the Premier League leaders.
Van Persie would be a risk considering he has only just returned from an ankle complaint, while Falcao has done little to convince fans that he would make an impact on the game. It doesn’t look good for United but they will still be confident of getting a good result given their excellent recent form.