The Polish centre-back was forced off at half-time of Tuesday's victory over Crystal Palace after taking a kick to the ankle and has not trained since.
Fulham could have midfielder Harrison Reed return for the trip to face his former club on the south coast.
Reed has been back in full training this week after suffering an ankle injury which has kept him out of the side since April.
Southampton provisional squad: Forster, McCarthy, Walker-Peters, Vestergaard, Stephens, Bednarek, Salisu, Ward-Prowse, Diallo, Ramsay, Jankewitz, Redmond, Armstrong, Minamino, Tella, Walcott, Djenepo, Adams, Ings, Obafemi, N'Lundulu, Ferry.
Fulham provisional squad: Areola, Tete, Andersen, Adarabioyo, Robinson, Anguissa, Reed, Cavaleiro, Decordova-Reid, Maja, Mitrovic, Lookman, Rodak, Hector, Ream, Bryan, Onomah, Aina, Loftus-Cheek, Carvalho.