Ederson, Walker, Stones, Fernandinho, Angelino, Gundogan, Bernardo, De Bruyne, D Silva (c), Aguero, Sterling
Subs: Bravo, Jesus, Mendy, Mahrez, Cancelo, Otamendi, Foden
John Stones and Fernandinho will form the central defensive pairing from the start for only the second time this season - the first being against Aston Villa last weekend.
Angelino is preferred to Benjamin Mendy at left-back, with Kyle Walker again getting the nod over Joao Cancelo.
Ilkay Gundogan will resume the anchor holding role, with Kevin De Bruyne and David Silva ahead of him in midfield.
Raheem Sterling and Bernardo will flank 12-goal Aguero in attack.
Same again, Blues
City know there can be no slip-ups as the pursuit of Liverpool continues.
With the top two teams both kicking off at the same time today, the Merseysiders will start the day six points ahead of the Blues.
Next weekend, Liverpool host the champions at Anfield and it is crucial we go there with the gap no more than six - and if Aston Villa can take anything against Jurgen Klopp's men this afternoon, the Blues must capitalise.
Playing teams back-to-back is never easy, but neither City or Saints will have the same starting line-ups, so in effect, it's like a different game.
Should Southampton play deep and try and catch the Blues on the counter, the longer the game is 0-0, the more dangerous the opponents' tactics will become.
If, however, City can go into the break a couple of goals to the good, it could be a long afternoon for the south coast side.
The last meeting...
Stats and facts
Southampton have lost nine and drawn one of their last 10 visits to the Etihad.
City's next goal will be the 50th in all competitions this campaign in just 17 games – we currently have 49 goals from 16 games at an average better than three per game.
Aguero has eight goals from just nine shots in the Premier League.
It is 15 years since Southampton kept a clean sheet in this fixture - a 0-0 draw at St Mary's in 2004.
The Blues have gone 27 games and 11 years since losing to a side that has begun the day in the bottom three of the Premier League.
Kevin De Bruyne's nine Premier League assists this season is five more than any other player in the top flight.
Conditions will very similar to last week - light rain and light winds - all conducive to City's slick passing style.