The Frenchman came off injured during the defeat at Bournemouth last week and no timeline has been set on his return, which is a major worry heading into the Europa Conference League semi-finals.
Gianluca Scamacca is also out after undergoing surgery on a knee problem while Vladimir Coufal is a doubt.
There is better news, however, regarding the likes of Declan Rice and Tomas Soucek.
The midfield duo, along with Nayef Aguerd missed the loss at Manchester City on Wednesday through illness but have all returned to training and should be fit.
One win would surely be enough to keep the Hammers in the Premier League and recovering key players to play a United side beaten at Brighton in the week is a big boost.
West Ham predicted XI: Fabianski; Johnson, Ogbonna, Aguerd, Cresswell; Rice, Soucek, Paqueta; Benrahma, Antonio, Bowen.
