Where and When
The match kicks off at 19:45 BST on Tuesday 29 October at the Etihad Stadium.
You can also catch the game in full on Man City for TV within 24 hours of the final whistle.
For those fans living outside the UK, you can find out where you can watch the game around the globe courtesy of livesoccertv.com.
Oleksandr Zinchenko and Rodrigo are sidelined for the next month.
Fernandinho, dismissed against Aston Villa,, is suspended for this game.
Leroy Sane and Aymeric Laporte remain long-term absentees.
Ryan Bertrand, sent off against Leicester City in the Premier League,is suspended for this game
Moussa Djenepo and Cedric Soares are injured.
Ilkay Gundogan Preview
“It’s all about staying in a rhythm and obviously, we don’t want to go out of this competition.
“We want to stay involved in this cup for as long as possible and we will perform as well as we can against Southampton and that is our target.
“It’s up to the manager to choose 11 fit and ready players and then it’s all about us all doing our jobs.
“We have won our last three games since the international break and we want to keep that momentum going.”
Referee: Jonathan Moss
Assistants: Simon Bennett and Edward Smart
Fourth Official: Darren Bond
Last time out
City overcame Aston Villa's resistance to triumph 3-0 thanks to goal from Raheem Sterling, David Silva and Ilkay Gundogan.
Sterling (2) and Aguero were also on the score-sheet in the meeting at the Etihad earlier in the 2018/19 campaign - a match the Blues won 6-1.