Midfielder James Ward-Prowse filled in at right-back during the closing stages of the defeat by Wolves, with Jan Bednarek and Jack Stephens other options for cover along with 20-year-old Kayne Ramsay.
Alexandre Jankewitz is available again following the midfielder's suspension for a red card in the 9-0 defeat against Manchester United, but Theo Walcott (thigh) and Ibrahima Diallo (muscular) remain sidelined. Michael Obafemi and Will Smallbone are long-term absentees.
Tammy Abraham should return after an ankle injury scare for Chelsea.
The England striker hobbled out of Monday's 2-0 Premier League win over Newcastle with a worrying problem, but has avoided any serious damage.
Southampton provisional squad: McCarthy, Stephens, Vestergaard, Bednarek, Bertrand, Romeu, Ward-Prowse, Redmond, Armstrong, Ings, Minamino, Forster, Ramsay, Salisu, Djenepo, Watts, Chauke, Jankewitz, Adams, Tella, N'Lundulu.
Chelsea provisional squad: Mendy, Azpilicueta, Zouma, Rudiger, Hudson-Odoi, Chilwell, Kante, Jorginho, Havertz, Ziyech, Giroud, Arrizabalaga, James, Christensen, Emerson, Alonso, Kovacic, Gilmour, Pulisic, Werner, Abraham.