Tottenham's Gareth Bale will return from paternity leave to face former club Saints on Sunday.
The Wales international missed the games with Chelsea and Maribor after the birth of his first child and will be joined in the squad by Brad Friedel, who also did not travel to Slovenia for yesterday's Europa League tie.
Emmanuel Adebayor could returns after back pain and be joined at St Mary's by Mousa Dembele, who has recently struggled with a hip complaint. Michael Dawson (illness) will be assessed, while Scott Parker (Achilles), Benoit Assou-Ekotto and Younes Kaboul (both knee) are all sidelined.
Provisional squad: Friedel, Lloris, Cudicini, Naughton, Walker, Caulker, Gallas, Dawson, Vertonghen, Smith, Livermore, Parrett, Dembele, Huddlestone, Sandro, Sigurdsson, Lennon, Townsend, Bale, Falque, Dempsey, Defoe, Adebayor.