Jose Mourinho saw his side dumped out of the cup on penalties after a 2-2 draw at home to Championship opponents, placing further scrutiny on the under fire manager.
Unbeaten in three after Wednesday's comprehensive 8-0 cup win over Macclesfield, the Hammers are priced at 3/1 (4.00) to extend their recent resurgence by pulling off a shock win in this one.
The sides shared a 0-0 draw when they met at this ground last season, and you can get odds of 13/5 (3.60) on them cancelling each other out once again.
Marko Arnautovic faces a late fitness test after picking up a knee injury against Everton last weekend, although Javier Hernandez is unlikely to be fully fit despite recovering from glandular fever.
Sergio Romero is suspended after getting sent off against Derby, although Marcus Rashford is set to return after completing his own three-game ban.
Having led the sack race betting after starting life at the London Stadium with four consecutive league defeats, Manuel Pellegrini has now been usurped by Mourinho following the Derby defeat.
However, that is not entirely down to the events at Old Trafford, with Pellegrini boosting his own job security thanks to positive performances against Everton and Chelsea, as well as an emphatic cup win.
The goalless draw with Maurizio Sarri's previously all-conquering team was particularly impressive, as West Ham managed to neutralise a team whose confidence could not have been higher.
With this in mind, they should back themselves to achieve a similar feat against the Red Devils, who have looked less than free-flowing in recent matches.
Having played out a goalless draw in their last league meeting here, even odds (2.00) look generous on no more than two goals being scored this time out given Manchester United's struggles.
Odds correct at the time of writing. Please gamble responsibly.