Manchester United captain Wayne Rooney will be out for up to six weeks with a knee injury, Press Association Sport understands.
The 30-year-old was left out of the 18-man squad that travelled to face FC Midtjylland in the Europa League on Thursday and Van Gaal explained why after arriving in Denmark on Wednesday.
"We have 13 players injured and Wayne is one of them," the Dutchman told MUTV.
"He has a knee problem so we have to wait and see. He scores a lot of goals so he is very important for us. We know that but we have to cope with that."
With United fifth in the league table, six points off the top-four, Rooney recently said that winning the Europa League or the FA Cup could save their disappointing season.
Combative midfielder Marouane Fellaini was another notable absentee and full back Matteo Darmian will not be involved after dislocating his shoulder during Saturday's 2-1 league defeat by Sunderland.
Van Gaal picked a young squad to face Midtjylland, including Regan Poole, Joe Riley and James Weir who could make their first-team debuts.
