United have won just once in the Premier League under Van Gaal, but appeared on course to kick-start their campaign when they led 3-1 after 57 minutes at the King Power Stadium.
However, the visitors endured a nightmare finale as Leicester scored four times to run out comprehensive winners, with United's day made worse by Tyler Blackett's dismissal and Jonny Evans' withdrawal due to a foot injury.
That setback leaves Van Gaal in need of a win to avoid back-to-back defeats for the first time in his reign and the former Netherlands coach has a big list of absentees for Saturday's home game against Sam Allardyce's side.
Blackett (suspended) and Evans join Chris Smalling (thigh) and Phil Jones (hamstring) on the sidelines, so Van Gaal could hand left-back Luke Shaw a debut at Old Trafford and move Marcos Rojo into the centre of defence.
Ashley Young (groin) and Jesse Lingard (knee) also miss out, while Marouane Fellaini and Michael Carrick remain on the sidelines with ankle problems.
The former Barcelona boss, who suggested this could now be the most difficult job of his career, has calmed fears over United's stuttering start.
"At the start we won all of our [pre-season] games but now we are in difficult circumstances. We should have won last weekend - we had to win when we were 3-1 up," he said on Thursday.
"If we had, we would have been two points off second place.
"But because of the loss you are now questioning me. If we won then it would have been different. We will overcome things - the season lasts a long time."
West Ham come into the game in fine spirits after a morale-boosting 3-1 win over Liverpool last Saturday.
Early goals from Winston Reid and Diafra Sakho laid the foundations for a victory which sees the London club occupy eighth place in the top flight.
As Allardyce seeks West Ham's first league win over United since 2007, the 59-year-old has a certain amount of sympathy for his opposite number.
"It takes time to get players gelling together. It's not an excuse, it's an actual fact," he said of United's slow start to the campaign.
"It takes time for everyone to get to know each other. United have already changed the system once to find a solution.
"They've got a few injuries, particularly defensive ones, so it's another opportunity for us to exploit.
"We are going into the game with confidence, and as underdogs. Hopefully we can go out and continue our good performances and get a result."
West Ham will be without Senegal international Cheikhou Kouyate (groin), while Saturday's fixture will also come too soon for Kevin Nolan (shoulder) and Matt Jarvis (thigh).
