The in-form Clarets return to Turf Moor to launch another run of key games.
Saturday’s sides are locked together on 23 points each – four points clear of the Premier League’s relegation places – with Southampton one place better off than Burnley thanks to a superior goal difference.
That demonstrates the importance of the game, while the Clarets also have to face Brighton and Newcastle United, both within touching distance, in two of their following three fixtures.
It will be a ‘one-game-at-a-time mantra’, however, from Burnley boss Sean Dyche, who has side back in the groove and unbeaten in five Premier League games.
The Clarets have drawn their last two away from home, including Tuesday night’s trip to Old Trafford, where Manchester United struck twice late on to deny Burnley a famous win.
Despite that disappointment, the display from Dyche’s side was as impressive as anything they have produced on the road this season.
And the boss is looking for a repeat to see off a Southampton team looking to steer clear of trouble under recently appointed manager Ralph Hasenhuttl and who entertain bottom-three sides Cardiff City and Fulham in two of their next three games.
“We are planning on delivering another good performance,” said Dyche.
“We are always aware of the opposition – you have to be – and they’ve had a good uplift since the new manager.
“But equally the focus on ourselves we have shown about performances is paying us back.
“We have to keep pushing our standards and keep delivering performances and then we have shown we have taken care of ourselves.”
New Burnley signing Peter Crouch could have a part to play against one of his former clubs.
The former England striker is match-fit and raring to go and may earn a place in the Clarets’ squad as the replacement for the departed Sam Vokes.
Winger Robbie Brady may also return after missing the mid-week trip to former club Manchester United with a groin problem.
But midfielder Steven Defour and defender Matt Lowton are not expected to return.
The Saints have no fresh injury worries, but remain without Ryan Bertrand, Mario Lemina and Michael Obafemi.
Former Clarets striker Charlie Austin stayed put at St Mary’s ahead of the transfer deadline but remains a doubt with an ankle problem.
Another former Burnley man, Danny Ings, will lead the visitors’ attack.
The Clarets extended their unbeaten Premier League run to five games in mid-week and return to Turf Moor looking for a third successive home league win and a fourth in five games.
Southampton appointed Austrian Ralph Hasenhuttl as manager in early December after sacking Mark Hughes with his side in the bottom three.
Since then, the Saints have won four times and lost just three times in the Premier League under the former RB Leipzig boss.
His only away defeat came at Cardiff in his opening game.
The two sides drew 0-0 at St Mary’s on the opening weekend of the season.
Southampton manager Ralph Hasenhuttl: “We know Burnley played a good game against Man United and nearly won.
“It’s the same against Burnley as it was against Crystal Palace – an opponent in our relegation battle who are fighting for every point.
“At the moment, the teams in this zone have a great mentality, because they know how important it is to take points, especially in these duels against opponents in their area.
“The game on Saturday and against Cardiff will be the toughest games for us.
"It's more important that we go unbeaten against these types of opponents."
If Burnley avoid defeat, they will equal the club record run of six Premier League games unbeaten.
The Clarets are unbeaten in five home league games against Southampton.
The Saints have won just one of their nine top-flight fixtures at Turf Moor.
Only Manchester United have a longer current unbeaten run in the Premier League than the Clarets.
Southampton have lost 15 points from a winning position this season - a figure matched only by Fulham.