Where to watch
Kick-off is set for 7:45pm BST. Live coverage of the game is available on Sky Sports 1 and Sky Sports 1 HD. Radio commentary is available on BBC Radio Live 5.
The Blues will now be hoping to get back to winning ways in the league following their 2-0 loss to Manchester United on 16 April.
With just four points separating Antonio Conte's men and Spurs, a win against Southampton would put early pressure on Mauricio Pochettino's side ahead of their visit to giant killers Crystal Palace on 26 April.
Chelsea will welcome back Gary Cahill who is training after suffering from gastroenteritis while Diego Costa and Eden Hazard, who were both rested in the FA Cup, are expected to be back in the starting eleven.
As for ninth place Southampton, the goal for the rest of the season will be to finish as high as possible in the Premier League.
Having played two less games than West Bromwich Albion, who are four points ahead with 44 points, eighth place is a realistic target for Claude Puel's men as the gap between the top seven and the rest of the Premier League is too great with just a month left in the season.
While an away trip to Chelsea will be a tough task, Southampton will have former Blues player Oriol Romeu back after a two-game suspension.
Sam McQueen however, is out with a minor groin strain while Charlie Austin will return to training this week.
What managers say
Antonio Conte: "I have in my mind the starting 11 but tomorrow I want to check very well the physical consideration of every single player as our last game was an intense one and used energy. But we have trained very well this season and we have a lot of energy to face this type of situation. It is important for us to win and look at ourselves, but we all know that tomorrow it won't be easy because Southampton is a very good team with a good coach and good players," via BBC Sport.
Claude Puel [on Oriol Romeu]: "I think he's not far off [N'Golo] Kante. He recovers the ball so well and is a technical player. He's an important player for this team because he can do fantastic work to recover the ball and start the play. It's difficult for us without him. We will see for the future, we are confident in him and, for me, he can look to getting in the selection with Spain, for example," via BBC Sport.
Betting odds (Betfair)
- Chelsea to win: 4/9
- Draw: 7/2
- Southampton to win: 17/2
Possible XI: Courtois; Azpilicueta, Luiz, Ake; Moses, Kante, Matic, Alonso; Willian, Costa, Hazard.
Possible XI: Forster, Soares, Yoshida, Stephens, Bertrand; Romeu, Davis; Ward-Prowse, Tadic, Redmond; Gabbiadini