The Saints recorded their first three points of the season with a 4-1 win over Aston Villa on Saturday, but they have lost four out of their five games back in the Premier League.
Wednesday, meanwhile, have tailed off after a solid start to the season – losing their last four - and sit just above the relegation zone with a return of seven points from seven games.
Southampton are expected to make changes from their win over Arsenal, but Maya Yoshida and Gaston Ramirez could both start in an attempt to build up their fitness. Meanwhile, Paulo Gazzaniga is expected to continue in goal at the expense of Kelvin Davis.
Sheffield Wednesday: WWLLLL
Southampton: Gazzaniga; Richardson, Seaborne, Yoshida, Fox; Guly, Ward-Prowse, Mayuka, Davis; Ramirez, Rodriguez
Sheffield Wednesday: Bywater; Semedo, Beevers, Gardner, Taylor; Miguel, Antonio, Barkley, Johnson; Bothroyd, Madine
Sports Mole says: 2-1