Tonda Eckert will be without both Flynn Downes and Kury Matsuki for tomorrow's quarter-final showdown with Premier League leaders, Arsenal.
Downes picked up a cheap yellow against Fulham in the previous round to add to the one that he collected at Doncaster Rovers in the third round.
Matsuki found his way into the same notebook as Downes. He too was shown a yellow at Doncaster and Fulham.
There are lingering doubts about the fitness of both LĂ©o Scienza (groin) and Jack Stephens (knock) ahead of Saturday evening's fixture.
Predicted Southampton lineup (4-1-4-1) or (4-3-3)
Goalkeeper and defenders
Goalkeeper - Daniel Peretz: Southampton’s best goalkeeper in years has helped transform the club's fortunes. Saints will need another big performance from the Israeli keeper.
Right back - James Bree: The English full back has been brilliant since returning from his loan at Charlton, and suits the profile Tonda Eckert needs on the right-hand side. Bree will need to be at his best to keep Gabriel Martinelli quiet.
Centre back - Taylor Harwood-Bellis:Â The first defender on the team sheet, Harwood-Bellis captained Saints to the 1-0 cup upset at Fulham in the last round. Gabriel Jesus offers a different type of test to the Championship strikers that THB has become used to playing against of late.
Centre-back - Joshua Quarshie:Â Jack Stephens looks doubtful, so Eckert could decide to rest his captain. Quarshie has Premier League pace, and this could be the deciding factor fo Quarshie over Nathan Wood.
Left-back - Ryan Manning:Â The chance to offer Max Dowman the benefit of his experience in the game will have the Irishman eagerly looking forward to it. Dowman, on the other hand, will fancy the test.
Midfielders
Centre midfield - Cameron Bragg:Â Flynn Downes' suspension is both a blessing and a curse. Downes has been in excellent form, and he will be essential for the crucial six-pointer at Wrexham on Tuesday. This provides Cameron Bragg with another chance to show what he can do in the anchor role, as he did against Coventry City.
Centre midfield - Caspar Jander:Â Jander is a Premier League player in waiting, and against Arsenal on Saturday, he will have the chance to prove it. Arsenal look likely to have Odegaard, Havertz, and Norgaard in the centre of midfield. For Jander, this is a huge test.
Centre midfield - Shea Charles:Â The Northern Ireland international could potentially become a world-class player in the future. During Northern Ireland's World Cup play-off defeat against Italy in the international break, Charles competed with the Azurri's best and came out on top.
Attackers
Right midfield - Tom Fellows:Â Kuryu Matsuki's suspension could present Tom Fellows with a great opportunity to show what he can do at the top level. Myles Lewis-Skelly will be keen to put down his claim for a regular starting spot at Arsenal, so it could be a very tough night for Saints out of form winger.
Left midfield - Finn Azaz:Â Eckert's teams rarely start without Finn Azaz in the starting eleven. Although Sam Edozie and LĂ©o Scienza will be pushing hard to play out on the left, the Saints boss could save both for minutes later in the game.
Striker - Ross Stewart:Â Cyle Larin might be a better option to deploy against Wrexham on Tuesday night, and he has been away on international duty with Canada. Larin played just 60 minutes across the two fixtures, being withdrawn after an hour against Iceland in a 2-2 draw.
Stewart should be fresh after the international break and keen to add to his winner against Fulham in the previous round.