Brighton boss Graham Potter confirmed 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.
Forward Aaron Connolly is not expected to return before the international break as he continues to deal with pain from a cracked rib.
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.
"Aaron Connolly has got a cracked rib, but he’s making good progress," said Potter. "We’re probably looking at after the international break for his return, that’s the only fresh one.
"Adam Webster is making good progress, again we’re looking at after the international break for him.
Of Lamptey, who has not featured since the 0-0 draw at Fulham last December, Potter added: "Tariq’s hamstring hasn’t responded as well as we’d like, so he will need surgery and will miss the rest of the season which is disappointing for him and for us.
"It’s incredibly disappointing for him as you can imagine. We tried things, but surgery is now the best option and we have to focus on getting him strong and ready for the start of next season.
"It’s a big blow for him – we have kind of got used to him not being available as he’s been out for a while. It’s disappointing for us though."
Brighton are desperate for points following their 2-1 home loss to Leicester last time out. It was Albion's third defeat on the bounce and they are above the relegation zone on goal difference only.
"To win would be fantastic, but there’s 11 games to go, a lot of points to play for and a lot of football to play,"said Potter.
"Every game is a massive opportunity to get something and we will do our best against a really good opponent. You can see the challenge of the Premier League, they’ve been on a tough run, but they were top of the league at one point.
"That’s the challenge we face, but we’re looking forward to it, we need to fight."
Southampton hope to have midfielder Moussa Djenepo available for Sunday’s Premier League.
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.
“It doesn’t look that bad so hopefully he can start training by the end of the week," said Hasenhuttl. "So he could be an alternative for the weekend but we don’t know it yet.
“Sometimes it feels worse than it is in the end, but when you scan him he immediately shows a lot of blood in muscles when he has odd injuries, so we have to pay attention to how tough the injury definitely is.
“This is not so easy for our physios to see clearly because sometimes he reacts better than they think.
“When he takes the test it looks better than it should be normally, so it is always tough to decide whether he is available or not.”
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