Manchester City boss Pep Guardiola has named the same starting line-up in three consecutive top-flight matches for the first time as a manager, but may opt for changes against Saints.
Kevin de Bruyne returned from injury in midweek and could play his first Premier League game for a month.
Phil Foden, who also made his comeback on Wednesday, awaits his first top-flight appearance of the season.
Southampton remain without Theo Walcott and Stuart Armstrong.
Will Smallbone has resumed training but lacks match fitness after nine months out with a knee injury.
Forward Shane Long, who tested positive for Covid-19 earlier this month, is back in contention.