Manuel Pellegrini's side has scored more in its last five matches than the Saints have all season, with Mauricio Pochettino's men facing a tough task to arrest a slump in form.
Mauricio Pochettino's men have lost three consecutive league matches for the first time under the Argentine, with their most recent defeat coming on Wednesday against Aston Villa.
The 3-2 loss was their first home reverse in the league this season, while it was also the first time that the Saints 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 but 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 scored 19 goals in that time - more than their hosts have netted all season.
Yaya Toure is among the top scorers for the visitors after he struck twice at the Hawthorns, and he voiced his pleasure after City recorded only their second away league win of the season.
"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 official 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 Saturday's game, with Matija Nastasic, David Silva and Stevan Jovetic (all calf) still remaining out.
Southampton will be out first-team regulars Nathaniel Clyne, Morgan Schneiderlin (groin) and Victor Wanyama (leg), while Jose Fonte is also a doubt. Paulo Gazzaniga will start in goal with Artur Boric (hand) out and Kelvin Davis still regaining fitness.