The influential Argentine striker has missed three weeks of action with a hamstring strain picked up in the Champions League last-16 first leg against Barcelona.
He admitted this week that he is wary of rushing back so as not to jeopardise his World Cup hopes, but reports on Thursday claimed that he was poised to be named in the 18 for the visit of the Saints.
In his absence, City's other forwards have scored only three times in eight games, although Yaya Toure's exploits in front of goal have kept them firmly in touch at the top of the table.
Manuel Pellegrini's side are four points behind new Premier League leaders Liverpool, having played two games fewer and knowing that a second championship in two years is still theirs for the taking.
Their opponents at the Etihad Stadium this weekend have had to deal with another week of speculation linking their boss and biggest names with moves away from Southampton in the summer.
Mauricio Pochettino has reportedly become Tottenham Hotspur's number one managerial target, while Liverpool maintain an interest in Luke Shaw and are believed to have joined the race for Adam Lallana.
Both will put these rumours to one side to start for the Saints in Manchester, but Maya Yoshida, Nathaniel Clyne and Kelvin Davis are missing, while Victor Wanyama faces a late fitness test.
Pochettino therefore may name an unchanged XI from the one that thrashed Newcastle United 4-0 at St Mary's Stadium, where Jay Rodriguez scored twice to enhance his England World Cup hopes.
Frenchman Morgan Schneiderlin is also hopeful of making it to Brazil, but may have to be content with a place on the bench, with James Ward-Prowse retained in midfield alongside Steven Davis and Jack Cork.
With the recovering Aguero yet to reach full fitness, Edin Dzeko is likely to continue as City's lone striker, with support coming from a trio of attacking midfielders and Toure in an initial holding role.
James Milner may be recalled at the expense of Jesus Navas, should Pellegrini want to give Pablo Zabaleta some extra defensive protection against the marauding runs of Shaw down the Saints left.
Victory would take the visitors to within three points of English champions Manchester United, who are seventh in the table, but City have only lost once domestically at Eastlands all season.
Recent form
Man City: DWWWLL
Southampton: WLWWLL
Possible starting lineups
Man City: Hart; Zabaleta, Demichelis, Kompany, Clichy; Toure, Fernandinho; Milner, Silva, Nasri; Dzeko
Southampton: Boruc; Chambers, Fonte, Lovren, Shaw; Davis, Cork, Ward-Prowse; Lallana, Rodriguez, Lambert
Source: www.sportsmole.co.uk
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