The Saints make the daunting trip to the Etihad Stadium on the back of a demoralising 9-0 defeat at the hands of Leicester City on Friday night.
While Pep Guardiola criticised the level of his team's performance against Aston Villa at the weekend, the Spaniard will be relieved that there has been no hangover in the aftermath of the defeat to Wolverhampton Wanderers before the international break.
A total of 10 goals and two clean sheets have come from fixtures against Crystal Palace, Atalanta BC and Villa, with the only effort against them coming from the penalty spot.
Bigger tests await during November with games versus Liverpool and Chelsea coming in quick succession, and Tuesday's EFL Cup tie will be an opportunity for some of the fringe players to stake a claim ahead of the high-profile fixtures in the coming weeks.
Having been provided with opportunities against Atalanta and Villa, Phil Foden will be keen to build on those outings as he bids to avoid dropping back down the pecking order like earlier in the campaign.
As for Southampton, back-to-back matches against City could not have come at a worse time, and Ralph Hasenhuttl will naturally have concerns heading into this contest.
However, the Austrian will perhaps be happy that his players have the chance to get their 9-0 drubbing against Leicester out of their system away from the Premier League, ahead of another trip to the Etihad at the weekend.
Hasenhuttl may have initially planned to play some of his squad players on Tuesday night, but that may now not be the case given the circumstances of their previous outing.
The Saints have also only recorded one win from their last six games, which came away at rivals Portsmouth in this competition, and it is a run of form which needs to change sooner rather than later if the club are to avoid becoming a constant fixture in a relegation battle.
Manchester City form: WWLWWW
Southampton form: LWLLDL
Man City will be without Fernandinho on Tuesday night after the Brazilian was dismissed during the latter stages against Villa.
Despite this competition being low on City's priorities, the likes of Kyle Walker, Nicolas Otamendi, Riyad Mahrez and Sergio Aguero may all start having begun the game at the weekend on the substitutes' bench.
Southampton are forced to make at least one alteration, with Ryan Bertrand serving a suspension for his red card against Leicester.
Manchester City possible starting lineup: Bravo; Walker, Garcia, Otamendi, Angelino; Gundogan, Foden; Mahrez, Bernabe, Sterling; Aguero
Southampton possible starting lineup: McCarthy; Stephens, Yoshida, Vestergaard; Valery, Romeu, Hojbjerg, Armstrong, Danso; Adams, Long
We say: Manchester City 4-1 Southampton
While Guardiola will no doubt ring the changes for this contest, City should still be too strong for their opponents on Tuesday night, who may feel like it is damage limitation even before the opening whistle.