David Moyes is likely to turn to Darron Gibson or Steven Pienaar to replace Jack Rodwell tomorrow afternoon.
Rodwell was substituted in the second half at Selhurst Park last weekend and while his hamstring injury is not as bad as first feared, he will not be available to play against Southampton.
Gibson replaced him in the capital and looked very assured on his debut, moving the ball well and adding some composure and experience in midfield.
Moyes was impressed by his performance and thinks he is more than ready to start.
He may, however, be temped to go with Steven Pienaar, who regularly played in a midfield three earlier this season. John O'Shea and Adnan Januzaj should be fit to play.
Moyes said: "Adnan and John O’Shea have done a little bit of training, I’ll need to check on them in the morning, see how they are. Jack Rodwell’s got a slight hamstring strain, not as bad as we first thought but we he won’t be available for this game.
"I think he’s [Gibson] ready. I don’t know if he’s ready to play 90 minutes but I think he would probably be a similar replacement (for Rodwell). Also I’ve got a question make over Steven Pienaar as well, who makes the team play in a different way.
“We’ve got to watch that we don’t get completely pigeon-holed into one way of playing and nothing else. I’ve got to be flexible so the opposition don’t find ways of nullifying us or we have no threat.
“I’ve got to be able to change.
“They’re the decisions I’ll make on the day."
The injury to Rodwell is a big blow after a big improvement in his performances in recent weeks. He and Didier Ndong were impressing as a pair in the centre of midfield and Rodwell's curse of not winning a league game after starting was finally lifted.
Moyes says the injury took the gloss off that moment but the Black Cats boss is encouraged by his recent displays.
He said: "I’d like to say he was celebrating but obviously the record isn’t something he would want. I think for Jack the biggest thing is he’s been playing well, he’s showing that the is a good player.
"I’m on his case at the moment, because I think he’s getting to an age where he has to start taking bigger responsibility, doing the right things more often, getting on the ball more often, and he’s just started to show it, so it’s unfortunate for him but hopefully it won’t be too long."