Ralph Hasenhüttl will be without his familiar full-back pairing when facing Arsenal at St Mary's on Tuesday evening - the second time the Gunners have visited the south coast in the space of four short days.
Saints were triumphant in the FA Cup at the weekend, but the manager is expecting to face a different Arsenal side in league competition, and will have to do so with half of his regular back four sidelined.
Ryan Bertrand misses out through suspension, having collected five yellow cards this season, while Kyle Walker-Peters has sustained a muscle injury in training and is unlikely to feature.
Speaking about Walker-Peters, Hasenhüttl commented: "It looks that he can definitely not make it tomorrow - this is another setback for us, to be honest.
"It's the quad area, he's got some problems. He only warmed up a little bit today and then felt some problems so had to stop.
"After Ryan Bertrand out with his fifth yellow card, we have to find the right solutions at full-back. It's an important position for our game."
The manager also provided an update on Saints' longer-term absentees, with both Nathan Redmond and Oriol Romeu nearing a return.
"The only good news is that Reddie [Nathan Redmond] is back, he will sit tomorrow on the bench. Maybe he is not ready yet to be an option, but he's trained with the team today.
"Ori is coming back, but it's a bit too early for him. Maybe the weekend. Over the next couple of weeks it will look a little bit better which is important, because we have a lot of games."