West Ham are missing forwards Jarrod Bowen and Michail Antonio with knee injuries suffered during the international break for their Europa League trip to Backa Topola.
Their absence means boss David Moyes may need to start teenage striker Divin Mubama in Serbia.
The Hammers will seal their place in the knockout stages if they win.
"Jarrod hasn't travelled and we've got another couple who have some illness," said Moyes.
West Ham and Freiburg - who they meet in the final game - are level on nine points at the top of Group A. The winner of the group reaches the last 16, with the runner-up going into a play-off round against third-place finishers in the Champions League group stage.