Ryan Fredericks will miss the rest of 2018 after sustaining an injury to his left fibula, Sky Sports News understands.
Right-back Fredericks suffered the injury shortly after coming on as a second-half substitute in the 1-1 draw with Huddersfield on November 10.
The 26-year-old, who joined West Ham from Fulham on a free transfer in the summer, has already begun a course of rehabilitation with a view to returning early in 2019.
Fredericks has made six appearances since arriving at the London Stadium, scoring his first goal for West Ham in the 8-0 Carabao Cup victory over Macclesfield in September.
Pablo Zabaleta has been preferred at right-back by manager Manuel Pellegrini for much of the season, but the injury to Fredericks leaves the 33-year-old Argentinian as West Ham's only recognised senior right-back.
Fredericks joins Manuel Lanzini, Andriy Yarmolenko, Winston Reid and Carlos Sanchez on the sidelines.
But West Ham will welcome back Mark Noble from suspension for the visit of Premier League leaders Manchester City on Saturday, while Andy Carroll and Jack Wilshere are closing in on their returns from injury.