A flurry of bookings in their 1-1 draw with Brighton & Hove Albion on Friday means Taylor Harwood-Bellis, Tyler Dibling and Flynn Downes will all be suspended here after amassing five yellow cards this season.
Downes absence is compounded by the fact fellow midfielders Will Smallbone and Adam Lallana are unlikely to recover from thigh injuries in time, and Lesley Ugochukwu is ineligible against his parent club.
Dibling will also be a big miss, as his performance against Brighton saw him named man of the match, and his stock grow further, with the 18-year-old already on the radar of some of the bigger clubs in England.
Martin's biggest problem is in goal though, because Alex McCarthy was culpable of handing Liverpool a goal in their 3-2 defeat just over a week ago, and that saw him dropped for Joe Lumley, who made his Premier League debut at the age of 29 against Brighton.
Lumley had a solid game at the Amex, and looks set to deputise while first-choice Aaron Ramsdale recovers from a setback that will keep him out until around Christmas, with Gavin Bazunu also set to miss most of the season.
Polish defender Jan Bednarek is doubtful following the knee injury he picked up on international duty last month, but Paul Onuachu could return after failing a late fitness test ahead of the clash with the Seagulls.
Ross Stewart is more than likely going to miss out though, with the Scot still a week or two away from making a full recovery.
Southampton possible starting lineup:
Lumley; Sugawara, Walker-Peters, Wood, Stephens, Manning; Fraser, Aribo, Mateus Fernandes, Armstrong; Archer