This match was originally due to take place in December, but Chelsea’s involvement in the World Club Cup means that this game will be played almost a month on from its original date.
In that time of course, the two teams met at St Mary’s in the FA Cup ten days ago, with the Blues serving up a reminder of why they are the current holders of that competition, with a 5-1 win on the south coast.
This league fixture is different prospect however, as Saints make their first trip to the Bridge since 2004 where they will be hoping to fare better than the 2-1 defeat in the season that would prove to be their last in the top flight for seven years.
The Cup exit aside, Nigel Adkins’ men are in good form. Just two defeats in the last eleven Premier League fixtures, with those losses only secured by a one goal margin.
Saturday’s win at Aston Villa has pulled Saints up to 15th in the table, with this midweek trip to West London a chance to make further ground on the teams around them, who have all played a game more.
Although Chelsea currently sit third in the league, they have stumbled at home of late. A defeat to QPR was followed up by a Capital One Cup loss to Swansea at Stamford Bridge, with those matches coincidentally being on Wednesday nights.
The game will be one that Saints star Jack Cork will be looking forward to. The midfielder spent over a decade with the Blues as a youngster, and although he never featured in a first team game for them, he remains close to a number of Chelsea players including young England full back Ryan Bertrand.
Petr Cech, John Terry and Frank Lampard are survivors from the last clash between the two teams at Stamford Bridge in the Premier League during 2004 which the Blues won 2-1.
Southampton will be without José Fonte and Adam Lallana who miss the trip through injury. Striker Emmanuel Mayuka has already linked up with Zambia ahead of the African Cup of Nations.
Luke Shaw is the only fresh worry for the visitors, with the full back having been stretchered off in the closing stages of Saturday’s game at Villa Park.
The Blues are likely to turn to Demba Ba in attack with Fernando Torres struggling through an illness.
John Terry is expected to be in the squad, but unlikely to start as he works his way back from a knee problem.
Nigeria duo John Obi Mikel and Victor Moses are unavailable as they are at the Africa Cup of Nations
Ten days ago, Chelsea were 5-1 winners in the FA Cup third round tie at St Mary’s. Demba Ba was on target twice for the visitors, who beat Saints for the first time in eight attempts in that comeptition.
This was a regular league fixture in the top flight until 2005 though Saints’ last win at the Bridge came in 2002 with a 4-2 success in West London.
Since then Saints have tasted two defeats and earned a draw at the home of the Blues.
Wednesday's game is the 88th all-time meeting between the two teams. Chelsea have the upper hand with 36 victories to Saints’ 26. A further 25 games have ended all square.
Michael Oliver will referee the game, and he will be assisted by Mr S Burt and Mr P Kirkup. Howard Webb is the fourth official.
As with every First Team game, we'll be providing minute-by-minute coverage throughout the day on our official Twitter
feed plus goal updates on our official Facebook
You can listen to live commentary courtesy of BBC Solent on Saints Player
, where you can keep up to date with all the stats and scores from around the country.
First Team Manager Nigel Adkins spoke ahead of the game, and you can read his pre match thoughts on saintsfc.co.uk