Gary Cahill missed the FA Cup semi-final against Tottenham due to illness and could be a doubt once again. Eden Hazard and Diego Costa are expected to be restored in the starting XI but Conte faces a selection dilemma with Pedro and Willian battling for the lone remaining forward role.
Southampton have Oriol Romeu returning after suspension but Alex McCarthy, Virgil van Dijk and Matt Targett remain out. Charlie Austin is nearing a return but the trip to Stamford Bridge is expected to have come too soon.
Get team news, match facts, quotes, odds and more ahead of the Premier League clash between Chelsea and Southampton.
Antonio Conte has cranked up the mind games with title rivals Tottenham Hotspur after his side's win over the same opponents in Sunday's FA Cup semi-final at Wembley.
See alsoChelsea v Southampton: LIVE
Conte's Chelsea were handed a quite usual Saturday to Tuesday turnaround this week, with a game against mid-table Southampton next up.
But Conte is not happy with the scheduling and believes (or at least says he believes) that it hands chasing Spurs a huge advantage:
" This week is crucial because they (Spurs) have an advantage and we have to play after two days. They have to play against Crystal Palace, who also have to play on Sunday. Tottenham also have one more day to rest and we play a team against a team that has 10 days to rest. Sometimes it is very difficult to understand, but we have to try to answer on the pitch. It is not easy to understand. At the start of the season you must try to have a balance and put both teams in the same position to fight. But we need to make the best answer on the pitch."
Chelsea go into the midweek games still four points clear of chasing Spurs, but held a ten-point lead going into April and have looked more vulnerable in recent weeks.
Conte's side have played fewer games this season than any of the other top four contenders - seven fewer than title rivals Spurs.
Willian (FC Chelsea vs. Tottenham Hotspur)
Willian (FC Chelsea vs. Tottenham Hotspur)Getty Images
Gary Cahill is a doubt for Chelsea due to illness, while Southampton are expected to still be without the injured quartet of Virgil van Dijk, Charlie Austin, Alex McCarthy and Matty Targett.
Antonio Conte: "I think that now at Chelsea we are in a period of transition. In this season, we have lost Ivanovic, Mikel and next season we lose John Terry. We are talking about players who wrote the history of this club. Now we have to find the right substitutes for these players and then work to put these players at the same level."
Claude Puel (on Oriol Romeu): "I think he's not far off Kante. He is very important for us. He recovers the ball so well and is a technical player. If we see the quality of his games since the beginning of the season, N'Golo Kante brings the same qualities as Oriol for us because he's very consistent and in every game he gives good performances, with consistency and quality."
Chelsea have lost just one of their last seven Premier League games at Stamford Bridge against Saints (W3 D3 L1), though this was last time out (1-3 loss in October 2015).
The Blues have scored in 15 of their 17 Premier League home games against Southampton, only failing to score in April 1995 (0-2 defeat) and December 2002 (0-0 draw).
Diego Costa has been directly involved in a goal in each of his last three Premier League appearances against Southampton (two goals, one assist).
Costa is now on a five-match run without a goal in the Premier League; his longest goalless streak in league competition since a six-game run between December 2012 and January 2013 in the Spanish Liga with Atlético de Madrid.
After losing just one Premier League match in six months between October 2016 and March 2017 (W19 D2 L1), Chelsea have already lost two games in April (W2 D0 L2).
The Blues haven’t lost three Premier League matches in the same month since October 2015 under Jose Mourinho – one of which was versus Southampton at Stamford Bridge.
The only previous occasion that Antonio Conte has lost three top-flight league matches as a manager in the same month was in November 2009 for Atalanta.
Southampton have won three of their last four Premier League away matches (W3 D0 L1) – more than they had in their previous 12 league games on the road in 2016-17 (W2 D3 L7).
Chelsea have gone 10 Premier League games without keeping a clean sheet for the first time since December 1996 (13 games).
Eden Hazard has been involved in 14 goals in his last 17 Premier League appearances at Stamford Bridge for Chelsea (11 goals, three assists).