Adam Lallana, who was struggling with a groin issue ahead of Liverpool, was introduced as a second half substitute for Aaron Connolly but lasted just eight minutes.
The former Southampton and Liverpool man immediately felt the injury and raced back down the tunnel for treatment and was replaced by Alireza Jahanbakhsh.
Albion head coach Graham Potter believes Lallana's swift departure against Liverpool saved him from a longer term injury and his absence will now be a couple of weeks rather than months.
"Adam lallana will miss the game," said Potter. "He is probably going to be a couple of weeks, I think. So it is not too bad.
"It is a little bit of a setback but it's nothing too serious which is positive. He is recovering well and getting on with his rehab."
Neal Maupay is also an injury doubt after he tweaked his hamstring moments after missing a first half penalty against Liverpool.
Albion's top scorer participated in light training this week and Potter will take a late decision on his striker.
"He has been with the physios this week. He has a chance to train on Saturday, so we will take a decision later on in the week for him.
"You are always a little concerned but it seems like it wasn't too bad. So that's a positive for us and a positive for him."
The Southampton match will also come too soon for Brighton midfielder Davy Propper. The Dutch international is yet to feature in the Premier League for Albion this season and continues to work his way back to full fitness after Achilles problems and illness.
It's a similar situation for Alexis Mac Allister. The Argentina international has not been involved since the defeat at Tottenham and is building up his fitness levels after an unconfirmed case of coronavirus.
The Monday night clash against sixth placed Southampton will see the return of fans to a Premier League match at the Amex Stadium for the first time since February.
2,000 supporters will be allowed through the turnstiles and Potter believes it's a huge boost for everyone involved.
"We hope everybody thinks it’s a positive," said Potter. "Clearly it’s a step in the right direction, and we’re excited for it.
"Looking forward to seeing them again, the event in the summer (Chelsea test match) was really positive and I think the players really enjoyed it.
"Hopefully we can put on a good performance and we can give them something to cheer, but it’s just great to have them back after so long."
Southampton have impressed this season and despite blowing a two-goal lead in the 3-2 loss to Manchester United last week Ralph Hasenhüttl's team will provide a serious challenge for 16th placed Brighton.
The have registered victories on the road at Burnley and Aston Villa and have claimed maximum points at home against West Brom, Everton and Newcastle.
"They’ve carried on the good work that they’ve done in the last year," said Potter. "They’ve been really really impressive, not just the points they’re getting, but the performances.
"I'm particularly impressed with the job that Ralph has done there, because they faced a really really tough moment last season and managed to get through it.
"I think that tells you a lot about the quality there. All credit to them for that, I like them a lot, I like the way they play, it’s really clear, it’s a good organised team, with some really good players, and we know it’s going to be a really tough game."