A home win would take City just three points behind Southampton and see the Bluebirds back into a tight knit top 6. A home defeat would leave City just a point off the play off places but six away Southampton who would pull clear.
Southampton are expecting to bring a crowd of around 1700 so it should be a decent atmosphere.
Cardiff are without a number of key players after injuries dominated last Sunday's game with Leicester.
The Bluebirds saw midfielder Craig Conway (ankle), defender Mark Hudson (ankle) and strikers Robert Earnshaw (thigh) and Rudy Gestede (hamstring) all pick up knocks during the goalless draw.
And the quartet join centre-back Ben Turner and Dekel Keinan (ankle) on the casualty list.
Playmaker Stephen McPhail may be fit after suffering a hamstring injury last week while Andrew Taylor is also hoping to be considered, but manager Malky Mackay has been trawling the loan market for temporary replacements. Joe Mason is expected to start up front with Kenny Miller.
Meanwhile, Safee Sali - dubbed the Malaysian David Beckham - has left the club after his two-week stay.
Sali had been training with Cardiff to get an idea of British football, and has been invited to return to the club for another two-week spell in the near future.
Dan Harding, Radhi Jaidi and Lee Barnard are back in contention for Southampton's trip to Cardiff.
Harding has missed the last four matches after jarring his knee in training but is fit again and set to challenge Dan Fox for the left-back spot.
Centre-half Jaidi (knee) and striker Barnard (ankle) could be involved in the squad for the first time this season having finally resumed training.
Midfielder Morgan Schneiderlin may have played his way into the starting line-up after his goalscoring cameo as a substitute secured a 1-1 draw at Burnley on Saturday.
Defender Dan Seaborne is the only absentee as he continues to recover from the head injuries he suffered in an assault outside a nightclub earlier this month.
Kick off at CCS is at 7:45pm.
There will Twitter and Facebook updates during the game and reaction afterwards on this website and messageboard.