The Saints have lost nine of their last 11 matches while Brighton's poor recent run has seen them drop back into serious relegation trouble.
Albion boss Graham Potter will also be without key players as he confirmed forward Aaron Connolly is not expected to return before the international break as he continues to deal with pain from a cracked rib.
Tariq Lamptey will have to undergo surgery for an ongoing hamstring problem, which is expected to see him absent for the remainder of the season.
Adam Webster has been continuing his return from an ankle injury at the start of February and is also targeting a return after the international break.
"Southampton were excellent for periods against Manchester City midweek," wrote Owen in Bet Victor predictions blog."The final score was probably a bit harsh on the Saints and it could be argued that they deserved something from the game.
"That said, they have now lost nine of their last eleven matches, so it’s fair to say they need to pick up a win sooner rather than later.
"Not much better can be said for Brighton. Now on their worst run of form of the season, they are on a three game losing streak. It’s hard for me to side with either side here, so I’m going for a draw at St Mary's."
Southampton hope to have midfielder Moussa Djenepo available.
The Mali international was taken off during half-time of the 5-2 defeat at Manchester City on Wednesday night because of a groin problem, which is not as bad as initially feared.
Leading scorer Danny Ings remains sidelined as he recovers from a leg injury, but is expected to be back after the international break.
Forward Theo Walcott (thigh) and midfielder Oriol Romeu (ankle) continue their rehabilitation, while Michael Obafemi and William Smallbone are long-term absentees.
Southampton provisional squad: McCarthy, Bertrand, Vestergaard, Stephens, Salisu, Bednarek, Ward-Prowse, Redmond, Djenepo, Armstrong, Adams, Forster, Walker-Peters, Diallo, Ramsay, Watts, Minamino, Tella, N’Lundulu, Ferry
Brighton provisional squad: Sanchez, Veltman, White, Dunk, Burn, Gross, Bissouma, Mac Allister, Trossard, Lallana, Maupay, Moder, Jahanbakhsh, Alzate, Welbeck, Izquierdo, Tau, Steele, Propper, Zeqiri
Southampton v Brighton 1-1