Slaven Bilic has labelled Diafra Sakho’s thigh injury “a big blow” after the striker was ruled out for three months.
The Senegal international, who has scored five goals this season, will undergo surgery on Saturday.
Sakho suffered the injury as he attempted to shoot during the second half of West Ham’s 1-1 draw with West Brom last Sunday.
Andy Carroll, who recently recovered from an ankle operation, is likely to start in Sakho’s absence when West Ham travel to Manchester United on Saturday.
Sakho joins fellow attackers Dimitri Payet and Enner Valencia on the sidelines with injuries beginning to bite at Upton Park.
“It’s a big blow,” said manager Slaven Bilic. “Those three injuries happened to three key players, especially in the offensive part of our game.
“Of course Carroll is important. It’s him and (Nikica) Jelavic and (Michail) Antonio.
“With the three of them it’s a massive blow, but it’s a good chance for some of the other guys to step in and show their class.”
Bilic is hopeful that Ecuador forward Valencia will be available in a couple of weeks after an ankle injury, but French playmaker Payet is set to be sidelined until February.