Crystal Palace will check on Darren Ambrose and Dean Moxey ahead of the game.
Midfielder Ambrose missed Saturday's 1-0 win at his old club Ipswich after picking up a knock against Bristol City, and full-back Moxey has been sidelined with flu.
Striker Calvin Andrew will hope to be in the squad having not been involved since his goal helped knock Middlesbrough out in the last round.
Back-up goalkeeper Lewis Price, midfielders Jonathan Williams and Stuart O'Keefe and forward Jermaine Easter will also be in contention if, as expected, boss Dougie Freedman makes a few changes.
Left-back Lee Hills is still out with a knee problem and midfielder Alex Marrow is not ready to return after an ankle injury.
Southampton will be without Dean Hammond and Jose Fonte.
Midfielder Hammond is suspended after his red card in the 1-1 draw at Reading on Saturday and former Palace defender Fonte has a slight hamstring problem.
Nigel Adkins is expected to make further changes and is unlikely to risk midfielder Adam Lallana, who has missed the last three matches with a foot injury.
Another ex-Eagle, full-back Danny Butterfield, is set to figure while goalkeeper Bartosz Bialkowski, centre-half Aaron Martin, winger Lee Holmes and Saturday's goalscorer Steve De Ridder could also come into the starting line-up.
Striker Lee Barnard may make the squad for the first time this season after an ankle injury but defenders Radhi Jaidi (knee) and Dan Seaborne (head) are still out.