Van Gaal saw his 10-man United side beaten by rivals Manchester City at the Etihad Stadium last weekend, with Chris Smalling dismissed in the first half for a second bookable offence.
Marcos Rojo, United's other starting centre-back in the derby, was also forced to leave the field with a suspected dislocated shoulder, meaning Van Gaal is set to be forced into a reshuffle at the back this weekend.
Injuries have been an almost constant problem for the Dutchman early in his United tenure, with Michael Carrick - fit again following a lengthy lay-off of his own - one potential option to come into defence.
United were four games unbeaten prior to their derby defeat and Carrick is ready to slot in at the back if required to help get his side back on track.
"[Defence] is not something I have played [in] an awful lot. I have had spells of it over the years playing two or three or four games in a season," the England international said this week.
"If I need to play there then fine - I have not had a lot of football recently so I will play anywhere.
"I think we have different options and can play different formations. We have a good variety now. We just need to get players fit and have more options to choose from."
Palace lost home and away against United last term and head into this weekend's match sitting outside the Premier League relegation zone on goals scored.
Mile Jedinak was sent off as Neil Warnock's men went down 3-1 to Sunderland on Monday, extending their winless streak to four matches.
Warnock's week then got worse as he received a fine from the Football Association as a result of comments he made about referee Craig Pawson following a defeat to Chelsea last month.
Ahead of what promises to be a difficult trip to Manchester without captain Jedinak, Warnock is under no illusions as to the size of the task Palace face - even taking into account Van Gaal's defensive worries.
"We're not going to get a tougher place to go than Old Trafford without Jedinak. It will be interesting just to see how we get on without him," said the Palace manager on Thursday.
"We're going to be under pressure even with him in the team, so without him I'm looking forward to seeing how the lads cope because he is an important player for us.
"They [United] have got one or two problems but I think every club has problems here there and everywhere.
"No doubt they will solve those in January and spend a few more quid. But they've got some fabulous players.
"When you play against teams like Chelsea, Man City and Man Utd, you can’t say you can stop him and stop him. The threats are everywhere."
Ashley Young (groin), Phil Jones (calf), Radamel Falcao (calf) and Jesse Lingard (knee) are all set to remain unavailable for the hosts, while Jonny Evans (ankle) is also expected to miss out again.
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