After some brilliant form throughout February, Ralph Hasenhuttl's side has struggled this month, losing three Premier League games on the spin since beating West Ham 3-0 in the previous round of the Cup.
Defeats to Aston Villa, Newcastle and Watford give them a mountain to climb if they're going to bounce back and overcome Manchester City in this weekend's FA Cup quarter-final encounter.
Here's how the Saints could shape up...
1. Goalkeeper & defenders
Fraser Forster (GK) - Should be set for another start in goal as Alex McCarthy remains out of contention.
Kyle Walker-Peters (RB) - Could be deployed once more in his favoured right-back role, with Tino Livramento likely not ready to come straight back into the starting XI.
Jan Bednarek (CB) - Wasn't great against Watford last time out but will inevitably retain his place.
Mohammed Salisu (CB) - Was even worse against the Hornets, but is the favoured option alongside Bednarek. Can be outstanding on his day.
Romain Perraud (LB) - Scored one of the goals of the tournament against West Ham in round five - another missile into the top corner would be good.
Mohamed Elyounoussi (RM) - Has put in some really good performance in recent weeks and should be set for an eighth consecutive start in all competitions.
James Ward-Prowse (CM) - The club's talismanic skipper will inevitably lead his colleagues out once more.
Ibrahima Diallo (CM) - Oriol Romeu could be given a rest for this one, with the very capable Diallo taking his place at the heart of the side.
Moussa Djenepo (LM) - After a disappointing showing last time out, Stuart Armstrong might be forced to sit this one out with the blistering Djenepo starting in his place.
Che Adams (ST) - In some solid individual form, with four goals and two assist in his previous ten across all competitions.
Adam Armstrong (ST) - Should return to the side in place of Will Smallbone, who started in his side's 2-1 defeat to Watford last time out.