A hectic holiday programme, including four games in 15 days, has taken its toll on United's squad and Van Gaal fears that many of his over-stretched players risk injury or burnout.
Defender Phil Jones is ruled out through injury while winger Ashley Young might not be risked with United set to face a Premier League clash at Newcastle United three days after playing third tier Sheffield United.
"Phil Jones is injured and a lot of players are in the red zone," Van Gaal, for once not grilled on his future as United manager, told a news conference.
"(Young) was back in training this week," Van Gaal added. "He is not injured, he is overloaded and in the red zone. More players are in the red zone and we have to decide if they can play against Sheffield United or not."
Young hobbled off against Swansea City last weekend, when United ended an eight-game sequence without a win to ease the immediate pressure on Van Gaal.
Midfielder Jesse Lingard is available, however, after recovering from a hamstring injury.
"He has trained fully this week so he is ready," Van Gaal said.
Van Gaal has only one more year left on his contract after the current season and Bayern Munich coach Pep Guardiola's name has been linked with the Old Trafford hot seat ever since the Spaniard said he would leave Germany at the end of the campaign.
Guardiola has also been touted as Chelsea's next manager, although bookmakers have him favourite to replace Manuel Pellegrini at Manchester City next season.
Van Gaal said he respected Guardiola's wish to coach in the Premier League, but said nothing should be taken for granted.
"It's not for sure he (Pep) will be the manager of a Premier club next season," he said. "I think that it is very good he wants to do that.
"I have already said that I am at the end of my career so for me it is not so interesting. For me, what is interesting is how I take care of Manchester United and I still have one year to go after this season."
(Reporting by Martyn Herman; editing by Toby Davis)
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