Mauricio Pochettino's men have lost three consecutive league matches or the first time under the Argentinian, with their most recent defeat coming on Wednesday against Aston Villa.
The 3-2 loss was their first home reversal in the league this season, while it was also the first time that Pochettino's charges had conceded more than one goal at St Mary's Stadium since April.
Having made a bright start to their campaign, Southampton have stuttered somewhat recently, taking just four points from their last possible 15 and they face a tough proposition in City.
Manuel Pellegrini's side are in stunning form at home and showed signs of replicating that on the road with a 3-2 victory at West Brom on Wednesday.
Southampton midfielder Adam Lallana is confident his team-mates can bounce back from their midweek disappointment.
"We've got a big game on Saturday – massive in fact. It's not that we're not playing well. We are playing well," he told the club's official website.
"We've got to prepare and get everyone as fit as we can. It is a big month. We've proved we can beat Man City. We did last season, so let's do it again."
City have won four of their last five Premier League matches and have had no trouble finding the back of the net, scoring 19 times in those top-flight outings - more than their hosts have managed all season.
Yaya Toure is among the top scorers for the visitors, with the Ivorian midfielder having struck a brace at the Hawthorns, and he voiced his pleasure after City recorded only their second away win of the season in the league.
"I think (it) was very important to take the three points. We know how difficult it is playing away and I think this will give us a lot of confidence for the next game," he told City's website.
"We have a tough game against Southampton on Saturday and we want to make a go of it there as well."
Southampton have won just two of their last six meetings with City in all competitions, although they tasted success in the corresponding fixture last season.
In February, the hosts' goals came from Jason Puncheon, Steven Davis and a Gareth Barry own-goal, while Edin Dzeko grabbed a consolation for the away side.
Pellegrini has no fresh injury concerns for the clash, with Matija Nastasic, David Silva and Stevan Jovetic (all calf) still missing, while Southampton could be handed a double boost - Victor Wanyama and Nathaniel Clyne in contention after knocks.
