We will host Russell Martin’s strugglers at 15:00 (UK) knowing that victory will earn us top spot for 24 hours at least before current leaders Liverpool face Arsenal on Sunday.
Meanwhile, Southampton are in search of their first win of the campaign having picked up one point from their eight matches so far.
We are unbeaten in our last 12 home league matches against Southampton, winning 10 and draw on that run and not suffering defeat since 2004.
Ahead of the latest clash with the Saints, we look back on some of the defining moments this fixture has seen through the years.
In 2018/19, this particular fixture saw Sergio Aguero become just the third man in Premier League history to score 150 goals with a single club.
However, the two goals that really resonate when this fixture is mentioned came from flying wingers.
First up, Georgi Kinkladze’s magical weaving run and chip at Maine Road in 1996 and then there’s Raheem Sterling’s winner at the death during the season of our first title success under Pep Guardiola.
Take a trip down memory lane by watching the video above...
City v Southampton app coverage
Our official app allows you to follow all of the action from the Etihad in one place.
Minute-by-minute text updates will begin in our Matchday Centre two hours before kick-off, while our Matchday Live show will begin slightly later than usual (approximately 13:55), due to our live City+ coverage of West Brom against our Elite Development Squad in Premier League 2.
Gareth Taylor and Andy Morrison will be the guests on the latest Matchday Live show, offering their expert insight before, during and after the action.
During the game you can also listen to live audio commentary from Alistair Mann and Steve Howey while our text commentary continues.
Make sure to have push notifications turned on as well, so you can be alerted to key moments in the action, including goals, red cards and the team news.
Short highlights from the match will be available from 19:00, whilst extended highlights from the encounter and a full-match replay [available on CITY+] can be accessed from midnight.
