Maurizio Sarri's men ended 2018 in strong fashion with four wins from their last five league games, and will aim to start the new calendar year as they mean to go on.
The Saints, meanwhile, remain embroiled in the fight to avoid relegation and despite two wins in their last four games, Ralph Hasenhuttl's side are still in trouble.
Chelsea lost their last home Premier League against Leicester City, which was only their third league loss at Stamford Bridge in 2018.
Olivier Giroud suffered suspected ankle ligament damage at Crystal Palace on Sunday, so joins Cesc Fabregas, Pedro and Ruben Loftus-Cheek on the sidelines. The injury to Giroud could mean some minutes for out of favour Alvaro Morata.
For the Saints, full-back Ryan Bertrand is expected to miss out once more along with striker Michael Obafemi, while Pierre-Emile Hojbjerg is suspended.
Though they are hovering just above the relegation zone, Southampton have been scoring with impressive regularity.
The side from the south coast have netted in nine of their last ten Premier League games, during which time they have scored against Manchester City (in two separate games), Arsenal, Spurs and Manchester United.
Scoring at Stamford Bridge could be a challenge, though, with Chelsea having conceded just eight times in ten league games in front of their own fans, a keeping clean sheet in three of their last four fixtures.
Tips and predictions
Opposing both teams to score has paid out in each of the last six matches at Stamford Bridge in all competitions and a repeat is offered at 8/11 (1.72).
For higher odds, consider backing both teams to score 'no' and under 2.5 goals at 19/10 (2.90) which has paid out in five of Chelsea's last six home clashes.