Southampton will be without suspended midfielder Oscar Gobern.
Gobern was sent off in Saints' 3-1 victory against south coast rivals Bournemouth and will now serve a three-match ban.
Frenchman Morgan Schneiderlin is out with a knee injury, leaving Dean Hammond and Richard Chaplow as the only fit central midfielders in the first-team squad.
Guly Do Prado is nearing a return to action after being sidelined by a hamstring injury for the past three weeks, but this game will come too soon for the Brazilian midfielder.
The same goes for Bartosz Bialkowski, who has not played since January following a knee injury he sustained in training.
Joseph Mills and Jason Puncheon are currently out on loan at Doncaster and Blackpool respectively.
Sheffield Wednesday's two new loan signings Danny Batth and Rob Jones are expected to go straight into the starting line-up.
Wolves defender Batth, 20, and fellow centre-half Jones, 31, from Scunthorpe, joined the Owls this week until the end of the season.
Another central defender, Mark Beevers, is out for the rest of the campaign after fracturing his cheekbone early in the midweek defeat to Peterborough.
Manager Gary Megson has promised several changes and confirmed striker Paul Heffernan will start, probably alongside Gary Madine, while versatile defender Lewis Buxton is pushing for a place in the squad following a long-term hamstring injury.
Megson, who has no new injury or suspension problems, could recall midfielder Chris Sedgwick to the squad as his side bid to avoid a third successive league defeat.