The Tottenham loanee will miss Saturday's encounter on the south coast, with Yan Valery likely to step into the breach.
Villa will be boosted by the return of Tyrone Mings.
The defender missed the home defeat to Tottenham with tonsillitis but he resumed on Wednesday and he is expected to be restored to the starting line up by boss Dean Smith.
Southampton provisional squad: McCarthy, Valery, Stephens, Vestergaard, Bertrand, Ward-Prowse, Hojbjerg, Armstrong, Ings, Long, Adams, Djenepo, Romeu, Obafemi, Smallbone, Gunn, Bednarek, Vokins.
Aston Villa provisional squad: Reina, Nyland, Sarkic, Guilbert, Engels, Konsa, Mings, Taylor, Drinkwater, Elmohamady, Luiz, Nakamba, Targett, Grealish, Trezeguet, El Ghazi, Hourihane, Jota, Lansbury, Samatta, Baston, Vassilev.