Southampton will again be without record signing Gaston Ramirez as he continues his recovery from a thigh injury.
Defender Frazer Richardson (groin) and midfielder Jack Cork (knee) are both out, but Tadanari Lee has recovered from his elbow injury and could feature.
Young defender Luke Shaw has overcome his illness and may make his Premier League debut.
Tottenham's Gareth Bale will return from paternity leave to face his former club.
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 Thursday's Europa League tie.
Emmanuel Adebayor could return 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.
Southampton (from): K Davis, Gazzaniga, Boruc, Butterfield, Stephens, Clyne, Fox, Shaw, Yoshida, Hooiveld, Fonte, Seaborne, Ward-Prowse, Do Prado, Chaplow, De Ridder, Lallana, Schneiderlin, Lee, Puncheon, S Davis, Lambert, Rodriguez, Mayuka.
Tottenham (from): Friedel, Lloris, Cudicini, Naughton, Walker, Caulker, Gallas, Dawson, Vertonghen, Smith, Livermore, Parrett, Dembele, Huddlestone, Sandro, Sigurdsson, Lennon, Townsend, Bale, Falque, Dempsey, Defoe, Adebayor.
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