The former Manchester United interim head coach watched on from the stands as Brentford thumped his side 4-1 on Saturday, a game in which Caleb Okoli had to come off early after colliding with his own goalkeeper.
There is still no indication of how serious the defender's issue is, but as Leicester only have 72 hours to recuperate from their trip to the Gtech Community Stadium, it would be a shock to see him line up here.
Abdul Fatawu (ACL), Harry Winks (groin), Ricardo Pereira (thigh) and Jakub Stolarczyk (ankle) are also unavailable for Van Nistelrooy's first game, where the Dutchman should call on Jannik Vestergaard to step in for Okoli in defence.
Caretaker boss Ben Dawson opted for three centre-backs at Brentford, but Van Nistelrooy has always favoured a four-man rearguard and will likely cut Conor Coady from the starting lineup in favour of an extra midfielder or attacker.
Luke Thomas can also expect to be culled as Victor Kristiansen returns to left-back duties, while either Bobby Decordova-Reid or Stephy Mavididi should benefit from a system change out wide.
Whichever winger gets Van Nistelrooy's thumbs-up should comprise an attack also featuring Jordan Ayew, Facundo Buonanotte and Jamie Vardy, who has not managed a goal against West Ham since 2019.
Leicester City possible starting lineup:
Hermansen; Justin, Faes, Vestergaard, Kristiansen; Ndidi, Soumare; Decordova-Reid, Buonanotte, Ayew; Vardy