De Gea has been strongly linked with a move to Real Madrid.
Van Gaal says on Friday “it is not easy for De Gea to manage his situation now,” and “he shall not play.”
De Gea’s absence means Sergio Romero, a preseason signing on a free transfer, could make his debut.
United may also be without defender Marcos Rojo and midfielder Bastain Schweinsteiger, another preseason signing from Bayern Munich.
Van Gaal says, “Rojo came (back) one week ago, Schweinsteiger came at the last moment, I don’t think that he is fit enough.”
Meanwhile, midfielder Ashley Young has signed a three-year contract extension.