Chelsea can move to within 4 points of Arsenal at the top of the Premier League and go into 2nd place if the Liverpool fail to beat Hull on Sunday.
Jose Mourinho’s side comprehensively beat London rivals West Ham 3-0 last weekend but were undone against Basel in the Champions League on Tuesday.
However, the Blues still qualified for the knock-out stages despite a limp defeat.
Southampton shocked Chelsea last season with a come-from-behind 2-2 draw at Stamford Bridge, Mourinho and his men will be hoping that history doesn't repeat itself on Sunday.
Mauricio Pochettino’s Southampton have performed above par this season and currently lie in fifth position, level on points with Manchester City in fourth.
Saints have only lost twice this season and could move into second place if results go their way this weekend.
Ricky Lambert’s four goals and three assists this season will mean that the Chelsea defence will have to stick to the England international like glue.
Striker Samuel Eto'o is to miss Sunday's Premier League clash with Southampton and is expected to be out for two weeks with a groin injury. The Cameroon forward sustained the grade one tear in
Tuesday night's Champions League loss at Basel and was replaced by Fernando Torres, who made his return from an abductor injury and could start at Stamford Bridge as Jose Mourinho rotates his options for the first of nine December matches.
The Saints clash could come too soon for defender David Luiz despite his return to training from a knee injury, while midfielder Marco van Ginkel, who is out with a knee injury, is a long-term absentee.
Chelsea manager Jose Mourinho insists he picked the wrong team to face Basel in the midweek Champions League tie.
Home fans will be hoping he gets it right against a Southampton side in the midst of their best start to a Premier League campaign.
After giving Arsenal what their manager Arsène Wenger described as their toughest examination of the season,
Mauricio Pochettino’s side should be strengthened by the return of centre back Dejan Lovren.
Mourinho, meanwhile, is unlikely to leave Eden Hazard on the bench this time.
Southampton will give a late fitness test to defender Dejan Lovren, who has been ill.
Luke Shaw is struggling with a thigh injury while Jack Cork is still sidelined with an ankle problem.
