Saints bested Championship side Sheffield United 4-2 on penalties on Tuesday evening after the score was level at 2-2 after 90 minutes.
Chelsea had to take a similar route to secure their position in the next round of the EFL Cup.
Thomas Tuchel’s side drew 1-1 at home against Aston Villa before defeating them in a penalty shootout on Wednesday.
The tie will take place on either Tuesday 26th or Wednesday 27th October at Stamford Bridge just weeks after the league fixture scheduled for 2nd October.
Chelsea - Southampton is one of five all-Premier League fixtures in the next round.
Here is the full Carabao Cup fourth round draw:
Chelsea vs. Southampton
Arsenal vs. Leeds United
Stoke City vs. Brentford
West Ham United vs. Manchester City
Leicester City vs. Brighton & Hove Albion
Burnley vs. Tottenham Hotspur
QPR vs. Sunderland
Preston North End vs. Liverpool