Chelsea's Ben Chilwell and N'Golo Kante will be monitored after withdrawing from international duty, while Edouard Mendy is set to miss out after injuring his thigh in training with Senegal.
Christian Pulisic and Hakim Ziyech should both be fit, with the latter in contention for the first time.
Theo Walcott could play his first game for Southampton since 2006 after rejoining the club on loan.
Another new signing, Ibrahima Diallo, is available for his debut.
Moussa Djenepo and Mohammed Salisu are both ruled out, while Stuart Armstrong will not be considered, although he is back in training after a period of self-isolation following a positive coronavirus test.