While the Citizens have picked up 10 points from their last four top-flight away games, the Saints have accumulated the same number of points across their 14 home matches this season - the fewest of any team in the division.
Match preview
After rescuing a point in a 3-3 draw at home to Tottenham Hotspur, Southampton came away from the London Stadium empty handed last weekend as they lost 1-0 against relegation rivals West Ham United.
Nayef Aguerd's first-half header proved to be the winning goal that condemned the Saints to their 18th Premier League defeat of the season, leaving them rooted to the foot of the table and four points adrift of safety.
Since taking the reins on a permanent basis, Ruben Selles has only won one of his six top-flight matches in charge of Southampton - a 1-0 home win over 19th-placed Leicester City last month - and they have failed to score in three of their last four games under his tutelage.
Indeed, the Saints have struggled to pose a regular threat in the final third and they are currently the joint-lowest scorers in the Premier League, finding the net just 23 times in 29 games along with Wolverhampton Wanderers and Everton.
However, Southampton managed to score twice in their last meeting with Man City, with Sekou Mara and Moussa Djenepo both on target in a 2-0 EFL Cup quarter-final victory at St Mary's in January.
Southampton have only won one of their last 13 Premier League meetings with Man City, but Selles will hope his side can replicate their resilient EFL Cup showing that frustrated the Citizens earlier this year as they bid to climb to safety.
Man City extended their winning run across all competitions to seven matches when they put an out-of-sorts Liverpool outfit to the sword with a deserved 4-1 victory at the Etihad Stadium last weekend.
Julian Alvarez cancelled out Mohamed Salah's opener, before Kevin De Bruyne, Ilkay Gundogan and man-of-the-match Jack Grealish capped off what was described by Pep Guardiola as "one of the best" performances in his seven years as manager at the club.
Guardiola's 100th Premier League home win momentarily saw the Citizens move to within five points of leaders Arsenal, but the gap to the summit increased to eight just a few hours later after the Gunners beat Leeds United. City could reduce the gap to five once more with a win over Southampton before Mikel Arteta's men travel to Anfield to face Liverpool on Sunday.
City, who beat Southampton 4-0 at the Etihad in October, head into Saturday's encounter having won each of their last 10 Premier League games against teams starting the day at the bottom of the table, a run dating back to March 2016, while they have not conceded in any of their last 14 fixtures against a basement club.
The Citizens can ill-afford to take Southampton lightly, though, having failed to win two of their last three visits to St Mary's including a 1-1 draw in the Premier League last season.
Guardiola and co will be keen to build their momentum by securing maximum points on the South Coast before turning their attention to next week's mouth-watering Champions League quarter-final tie with Bayern Munich.
Southampton Premier League form:
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W
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Southampton form (all competitions):
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Manchester City Premier League form:
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Manchester City form (all competitions):
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Team News
Southampton boss Selles has confirmed that Che Adams and Mohammed Salisu - who both picked up injuries during the international break - remain sidelined along with Valentino Livramento and Juan Larios, the latter of whom is ruled out for the rest of the season.
Armel Bella-Kotchap missed the defeat at West Ham after sustaining a shoulder injury just seven minutes into the draw with Tottenham, and the centre-back is still a "question mark" for Selles ahead of Saturday.
A back four of Kyle Walker-Peters, Jan Bednarek, Duje Caleta-Car and Romain Perraud is set to remain intact, while Romeo Lavia and Carlos Alvarez will battle to start in centre-midfield alongside captain and top scorer James Ward-Prowse.
Theo Walcott could be handed a third successive start in attack, while Mara may find his spot in the first XI under threat from either Kamaldeen Sulemana or Paul Onuachu.
As for Man City, Erling Braut Haaland returned to team training earlier this week after missing the win over Liverpool with a groin injury, and the Premier League's top scorer could be in contention to start at St Mary's.
Guardiola will likely manage Haaland's minutes, though, with one eye on next week's Champions League tie, so Alvarez could continue in attack after impressing against Liverpool.
Defensive trio Kyle Walker, Aymeric Laporte and Rico Lewis will all be looking to force their way back into the starting lineup after watching on as unused substitutes last weekend, while Bernardo Silva could be recalled to start in either centre-midfield or on the right side of attack.
Phil Foden remains unavailable as he recovers from appendix surgery, while De Bruyne could continue in the middle of the pitch alongside Gundogan and Rodri, and the Belgian playmaker will be looking to register his 100th Premier League assist.
Southampton possible starting lineup:
Bazunu; Walker-Peters, Bednarek, Caleta-Car, Perraud; S. Armstrong, Ward-Prowse, Lavia, Elyounoussi; Walcott, Sulemana
Manchester City possible starting lineup:
Ederson; Walker, Stones, Dias, Ake; De Bruyne, Rodri, Gundogan; Bernardo, Alvarez, Grealish
We say: Southampton 0-3 Manchester City
Despite suffering defeat in their last visit to St Mary's, Man City will be regarded as strong favourites to claim maximum points on Saturday and boost their hopes of closing the gap to leaders Arsenal.