Meanwhile, left-back Ryan Bertrand remains out of action with a calf injury, while his recent confirmation that he will leave the club at the end of the season suggests that the former Chelsea man may have made the last of his 213 combined appearances for the Saints.
In their absence, Jack Stephens should partner Jannik Vestergaard at the heart of the defence while Mohammed Salisu could again feature at left-back.
Alongside William Smallbone, key midfielder Oriol Romeu will also miss out, having suffered an ankle injury in February to rule him out for the remainder of the campaign, leaving James Ward-Prowse and Stuart Armstrong to operate in the middle.
Young winger Nathan Tella put forward his claim for a starting spot after he came off the bench last time out against Fulham to score the first goal of his Southampton career, potentially featuring on the opposite flank to Nathan Redmond on Tuesday.
Forward Danny Ings may be due a rest as Southampton approach their third league game in eight days, coinciding with his return from injury, but he could be handed a third start in a row despite his patchy injury record, given the front man's importance to the team.
He should be joined by Che Adams, who has netted in the last two matches to take his tally to nine top-flight goals this season.
At the other end of the pitch, Fraser Forster will line up in the Saints' goal with confidence, having kept them in the game with a penalty save against Crystal Palace last Tuesday, as the Hampshire side went on to win from behind.
Southampton possible starting XI: Forster; Walker-Peters, Vestergaard, Stephens, Salisu; Tella, Armstrong, Ward-Prowse, Redmond; Ings, Adams