Albion have lost their last three matches and badly need the points to help pull themselves clear of the relegation zone.
Potter will once again be without the talents of flying wing back Tariq Lamptey who will undergo surgery on his hamstring injury and has been ruled out for the season.
Defender Adam Webster (ankle) and striker Aaron Connolly (rib) will also miss the trip to St Mary's. Adam Lallana will hope to build on his impressive display in the 2-1 loss against Leicester last week and impress against his old club Southampton.
Scroll down and click through to see how Brighton could line-up at St Mary's.
1. Rob Sanchez
The Brighton keeper had his first major wobble in the defeat against Leicester last week. Graham Potter said he has trained well this week and has the character to put it behind him and be ready for Southampton
2. Joel Veltman
The Dutch international has been excellent in the absence of Tariq Lamptey and will likely take his role at right back
3. Ben White
The classy defender will slot in at centre back alongside Lewis Dunk in the absence of Adam Webster
4. Lewis Dunk
The skipper has been excellent for Brighton this season and will once again need to be at his best at St Mary's - even though Southampton striker Danny Ings is missing with injury