Goalkeeper Gavin Bazunu (Achilles) remains a long-term absentee, while head coach Russell Martin has confirmed that Kamaldeen Sulemana (ankle) is the only other player unavailable for selection.
Ben Brereton Diaz is fit to play in attack as his early withdrawal in Chile's CONMEBOL World Cup qualifier against Bolivia on Tuesday was a tactical decision and not a fitness one, while Ross Stewart has returned to training after a lengthy spell on the sidelines and is only lacking match fitness.
Former Manchester City defender Taylor Harwood-Bellis, Jan Bednarek and Jack Stephens are all set to continue in a three-man defence, with Kyle Walker-Peters and summer signing Yukinari Sugawara - who scored in the Saints' 3-1 loss to Brentford before the international break - expected to retain their places as wing-backs.
Fellow new recruits Mateus Fernandes and Adam Lallana will both be looking to force their way into the first XI, although Martin may decide to stick with Flynn Downes, Will Smallbone and Joe Aribo in midfield.
Brereton Diaz could be joined in attack by Adam Armstrong, but striker Cameron Archer may be handed his first start of the campaign after making three substitute appearances so far this term.
Southampton possible starting lineup: Ramsdale; Harwood-Bellis, Bednarek, Stephens; Sugawara, Fernandes, Downes, Smallbone, Walker-Peters; Brereton Diaz, Archer
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