Manuel Pellegrini has confirmed third-placed City will be without Joe Hart, Eliaquim Mangala, and Pablo Zabaleta as well as longer-term casualties Samir Nasri and Vincent Kompany however David Silva and Wilfried Bony are in the squad.
There will be key battles across the pitch which City will need to win in order to get back to winning ways, most notably in midfield.
Yaya Toure and Dusan Tadic will play important roles for their respective sides and their form will have a big say in who claims the points at the Etihad. So how do they match-up?
Yaya and Tadic have both made 12 Barclays Premier League appearances in 2015/16 so far clocking up 923 and 957 minutes respectively - the Saints’ Serbian spending just 25 minutes longer on the field than City’s Ivorian powerhouse.
Only Aleks Kolarov, Joe Hart, Fernandinho and Bacary Sagna have played more domestic minutes for City this season.
That said, Toure and Tadic have both been substituted seven times in that time.
As far as goals, they have five between them with Tadic edging Yaya by one - Toure’s strikes include a rocket of a shot at West Brom on the opening day of the season and then from the Etihad Stadium penalty spot against Norwich recently to claim a late victory.
The Ivorian has the slight upper hand when it comes to assists though with four so far to his name compared to Tadic’s three. Yaya sets up an opponent on average every 230 minutes compared to Tadic’s 319.
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