Leeds United manager Neil Warnock is expected to name a strong team after his side slumped to a 1-0 defeat at home to Birmingham City on Saturday.
The defeat was the club's third match without a victory and Warnock will be hoping his side can recapture the spirit that saw them beat Everton 2-1 in the last round.
Loan signing Ryan Hall is ineligible, while Lee Peltier, Rodolph Austin and Michael Tonge will undergo late fitness tests.
Tadanari Lee could return for Southampton after he recovered from an elbow injury.
Frazer Richardson and Jack Cork could also return after thigh and knee injuries, with manager Nigel Adkins likely to make several changes with his side taking to the pitch at Elland Road just over 48 hours after they lost 2-1 to Tottenham Hotspur.
Recent form
Leeds: WDWDDL
Southampton: WWLDLL
Possible starting lineups:
Leeds: Kenny; Peltier, Lees, Pearce, Byram; Austin, Pugh, Tonge, Norris; Becchio, Diouf
Southampton: Davis; Yoshida, Hooiveld, Richardson, Seaborne; Ward-Prowse, Cork, Guly, Chaplow, De Ridder; Lee
Sports Mole says: 1-2