Leading scorer Michail Antonio and goalkeeper Lukasz Fabianski will not be involved in West Ham's Europa League group game away to Rapid Vienna.
The Hammers have qualified for the knockout stage and will seal top spot in Group H with a win in Austria.
It is the first of three games in less than a week, with West Ham at Manchester City on Sunday before hosting Brighton next Wednesday.
"We're having to think ahead," said boss David Moyes on Wednesday.
Thursday's match is being played behind closed doors as Austria has returned to a full national lockdown to curb Covid-19 infections.