The Saints would climb above Manchester United into fifth in the table should they avoid defeat, while Chelsea could move into the top half for the first time since August.
European football appears to be an increasingly realistic prospect for Southampton again this season having seemingly begun to ebb away towards the end of 2015 and start of 2016.
The Saints suffered a spell of just one win and eight defeats in 10 matches in all competitions, a run of form that saw them slump as low as 13th in the Premier League table.
However, they have since turned things around completely and are now unbeaten in six matches, picking up a league-best 16 points from the last 18 on offer in the top flight.
That has seen them shoot back up to sixth in the table, with just one point separating them from fifth-placed Man Utd, who face Arsenal on Sunday. Ronald Koeman may even have one eye on loftier goals, with a win this weekend closing the gap on the Champions League places to just four points.
The turnaround in form has coincided with the return of Fraser Forster from injury, with the England goalkeeper still not having conceded a single goal in his six outings this season.
Southampton as a team have not conceded a Premier League goal for nine hours and 14 minutes, while you have to go back to before Christmas for the last time their defence was breached in a home league game, keeping four clean sheets in four consecutive wins at St Mary's and scoring 10 goals at the other end in the process.
Koeman's side have had two weeks to rest since their 1-0 victory over Swansea City in their last outing, when Shane Long got the only goal of the game, and should they return to action with a win or a draw then it would be their longest unbeaten streak in the league since 2013.
Recent form: WWWDWW
While Southampton have had a fortnight off since their last competitive action, Chelsea have been fighting on all fronts and impressing along the way.
The Blues took on the daunting task of travelling to the Parc des Princes last Tuesday for the first leg of their Champions League last-16 tie with Paris Saint-Germain and, while they lost 2-1 to the runaway Ligue 1 leaders, the performance gave cause for optimism.
The second leg of that tie does not take place until March 9, but John Obi Mikel's away goal in the French capital puts Chelsea in a decent position when they welcome PSG back to Stamford Bridge.
There was more to be happy with at the weekend too as the Blues took full advantage of Manchester City's weakened side to cruise to a 5-1 victory in the FA Cup, booking their place in the quarter-finals.
It was a result that maintained Guus Hiddink's 100% record in the competition, and the Dutchman is also unbeaten in the Premier League since his return to Stamford Bridge. Chelsea's run of 10 games without defeat is the longest current streak in the division.
Hiddink has only overseen three wins from his nine league outings in charge, but the last of those hinted at better things to come as they thrashed Newcastle United 5-1 having raced into a three-goal lead inside the opening 20 minutes.
All three of those impressive recent results have come at Stamford Bridge, but there is improvement to be seen away from home as well. Chelsea won just one of their eight league games on the road under Jose Mourinho this season, but since his departure they are unbeaten in four, during which time they have not even conceded a goal.
Should they continue that record with a win this weekend then it would be the first time all season that they have won back-to-back Premier League games.
Recent form: DDWDDW
Recent form (all competitions): WDDWLW
Chelsea captain John Terry will undergo a late fitness test to see whether he is able to return from the hamstring injury that has kept him out for the past two games.
Terry's centre-back partner Kurt Zouma is out for the rest of the season with an ACL injury, while at the other end of the pitch Radamel Falcao remains sidelined and Alexandre Pato is still working his way up to match fitness.
Diego Costa will lead the line again for the visitors, then, having scored seven goals in his last eight Premier League appearances.
Southampton are still without the services of the suspended Victor Wanyama following his third red card of the season against West Ham United earlier this month.
Southampton possible starting lineup:
Forster; Cedric, Van Dijk, Fonte, Bertrand; Davis, Clasie, Ward-Prowse, Mane, Long; Pelle
Chelsea possible starting lineup:
Courtois; Azpilicueta, Cahill, Ivanovic, Baba Rahman; Fabregas, Mikel, Willian, Oscar, Hazard; Costa
Head To Head
Chelsea have lost just one of their last seven Premier League trips to St Mary's, winning four of those.
Home and away, Southampton have only won two of their last 14 meetings with Chelsea, although they are unbeaten in their last three, including a 3-1 victory in the reverse fixture at Stamford Bridge in October.
Southampton have failed to keep a clean sheet in their last 12 games against the Blues, though, last doing so in a goalless draw at Stamford Bridge in 2002.
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We say: Southampton 0-0 Chelsea
Both of these teams are in good form coming into this match, including at the back, and they could cancel each other out this weekend. A draw would be seen as a satisfactory result for both teams, and we think that it could be a stalemate at St Mary's.