SAINTS and England goalkeeper Aaron Ramsdale is set to miss around a month of action after sustaining a broken finger in the 2-0 defeat at Wolves.
Defender Jan Bednarek is also ruled out of this weekend's clash with Liverpool and a further few weeks of action after a knee injury sustained with Poland.
Ramsdale, 26, missed Nations League clashes against Greece and the Republic of Ireland after withdrawing from the latest Three Lions international camp.
He is now likely to be sidelined for Premier League games against Liverpool, Brighton, Chelsea, Aston Villa and Spurs before Christmas.
Saints manager Russell Martin confirmed the shot-stopper underwent surgery last week, while Ramsdale has been spotted with a heavily bandaged hand.
Speaking ahead of Sunday's match, Martin said: "Aaron's had an operation on his finger so expect him to be back hopefully, this side of Christmas.
Every word Martin said on injuries, his PGMOL meeting, team shape and more before Liverpool.
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"Janny B is always the worry and the risk when they go away for an international break and one of the guys that you end up with has an injury.
"We spoke very quickly after the game and Janny was really worried about his knee. Thankfully the scan showed it's not as significant as we might have feared.
"He will be hopefully a week or two before Aaron, but they'll miss this small block of games and we'll do everything we can to get them back quickly.
"It's a massive blow ahead of what is a busy period as they've been two of our best players. They've been two of our best players all season."
Ramsdale has made nine Premier League appearances for Saints since his summer move from Arsenal, in a deal that could be worth up to £25million.
He kept his first clean sheet in the 1-0 win over Everton, in Southampton's final home match before the November international break.
Championship play-off hero Alex McCarthy will regain his place for the first time since August, after starting defeats against Newcastle and Nottingham Forest.
Martin added: "I'm excited for him. I have so much trust in Alex, we all do, and I really mean that. The guys see what a top goalkeeper is every day.
"I'm comfortable with Alex going in. He's done a brilliant job for us whenever he's played. At the end of last season, maybe we're not here if he doesn't perform.
"There was so much calmness and composure. If he came in a bit anxious, what he'd have done to the team... but he was immense.
"He's only not in the team because a goalkeeper all of a sudden wanted to come here after a lot of work, and it didn't look achievable at one point."
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