Daley Blind, Phil Jones (both ankle), Michael Carrick (calf) and Marcos Rojo (stomach) have been ruled out after suffering setbacks during United's derby victory over Manchester City last Sunday.
United travel to Stamford Bridge one point behind second-placed Arsenal – who are in FA Cup semi-final action this weekend - and could move within five of Chelsea if Van Gaal's injury-hit side can come away with a victory.
"It is the worst scenario," said the Dutchman. "Marcos and Phil can both play left central defender, and Jonny Evans is also suspended so I do not have many choices.
"Daley Blind and Michael Carrick could have played as holding midfields and I do not have another option. It is a puzzle."
However, the Dutchman does have Luke Shaw available and will give Robin van Persie as much time as possible to prove his fitness.
"Shaw I think is training for a lot of weeks already so he can play," he told MUTV. "Van Persie is another story - this is the first week he has trained with us, with the first team, but maybe we have to think about him."
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