Ian Holloway plans to make wholesale changes for Blackpool's trip to the League One outfit.
The Seasiders boss says most of his first-choice team will not even make the journey to St Mary's Stadium.
A number of fringe players and youth-team members are set to be given a chance.
Goalkeeper Paul Rachubka is likely to make his first start for a year while there could also be opportunities for the likes of Keith Southern, Dekel Keinan, Rob Edwards and Alex Baptiste. Brett Ormerod and Jason Euell could face their former club.
David Carney is at the Asian Cup with Australia while Elliot Grandin could be doubtful with a hamstring injury.
Southampton manager Nigel Adkins has almost a full-strength squad at his disposal for the game.
Winger Lee Holmes is the only absentee following his recent ankle surgery but Adkins reported no new injuries following Monday's win at Dagenham.
Adkins is expected to make changes with one eye on Saints' League One promotion push.
Striker Lee Barnard has made two substitute appearances since recovering from a hernia operation and he could be named in the starting line-up for the first time since mid-November.
Frazer Richardson, Morgan Schneiderlin and David Connolly will also be in contention along with Jason Puncheon, who is back at St Mary's following his loan spell at Millwall.
Blackpool (from): Rachubka, Phillips, Sylvestre, Grandin, Euell, Southern, Ormerod, Edwards, Baptiste, Halstead, Tomsett, Barkhuizen, Kingsley-Reynolds, Coid, Younda, Mitter, Martin, Dodd, Jobe, MacDonald.