Brentford could have a defensive headache.
Karleigh Osborne was taken to hospital with concussion following Monday's draw at Notts County, leaving the Bees with no fit centre-halves.
Pim Balkestein had already been ruled out for the season with an ankle injury and Leon Legge was missing with a groin problem.
Osborne remains a doubt but Legge was due to train by the end of the week and will be handed a late check.
Full-back Craig Woodman is struggling with a foot injury and goalkeeper Richard Lee (shoulder) and strikers Gary Alexander (knee) and Charlie MacDonald (ankle) are out.
Midfielder Adam Reed has extended his loan deal from Sunderland but defender Owain Tudur Jones has gone back to Norwich.
Southampton will still be without Alex Chamberlain and Lee Barnard.
Teenage winger Chamberlain and 16-goal striker Barnard are sidelined by ankle injuries and are unlikely to play again this season.
Midfielder Morgan Schneiderlin (knee) and winger Lee Holmes (ankle) remain long-term absentees but boss Nigel Adkins has no new injury concerns.
Left-back Dan Harding and midfielder Adam Lallana overcame groin problems to play in Monday's 2-0 win over Hartlepool and came through unscathed.
Radhi Jaidi, Danny Butterfield, Richard Chaplow and former Brentford defender Ryan Dickson are pushing for recalls after dropping out against Pools.
Saints remain in the second automatic promotion spot on goal difference from Huddersfield and with a game in hand.