While the Bees are looking to claim their third successive top-flight home victory, the Saints are out to record back-to-back away league wins for the first time since June 2020.
Match preview
After 20 games, few would have predicted Brentford to be sitting above the likes of Liverpool and Chelsea in the Premier League table this season, but Thomas Frank's side are placed inside the top eight on merit and they remain in contention to qualify for Europe, sitting just one point behind the top six.
The Bees were last in action two weeks ago when they played out a goalless draw away against Leeds United, a result which has extended their unbeaten Premier League run to eight matches - only Arsenal (22) and Newcastle United (18) have picked up more points than Frank's side (16) during this period.
With challenging away trips to Arsenal and Manchester United to come later this month, Brentford will be keen to take advantage of a favourable-looking home encounter against a Southampton side who remain rooted to the foot of the table.
Brentford have enjoyed plenty of success on home soil so far this season, accumulating 19 of their 30 points at the Gtech Community Stadium, including victories over Man United and Liverpool, and draws against Chelsea and Tottenham Hotspur.
The Bees eased to a 3-0 home win over Southampton in May last season, and another victory this weekend would see them secure back-to-back league wins against the Saints for the first time since March 1959.
Southampton have missed out on a place at Wembley in the EFL Cup final after losing 3-1 on aggregate against Newcastle United in the semi-finals, including a 2-1 second-leg defeat at St James' Park on Tuesday.
After an early Sean Longstaff brace seemingly put the tie to bed, a brilliant strike from Che Adams restored belief for the Saints on the half-hour mark, but the visitors ultimately came up short at the semi-final stage of a domestic cup competition for the third time in the last six years.
Nathan Jones's side will now look to dust themselves down and focus fully on their quest to avoid relegation from the Premier League, with Southampton currently sitting two points adrift from safety after winning just four of their 20 games so far this season.
The Saints have endured a torrid run of form in the top flight over the last few months, losing seven of their last eight matches, with their only victory during this period against fellow strugglers Everton.
Southampton have been boosted by the addition of five new signings in the January transfer window, and Jones is hoping they can make an instant impact, starting with Saturday's clash against Brentford, who the Saints have beaten in two of their last three league meetings including a 4-1 home victory last season.
Brentford Premier League form:
W
D
W
W
W
D
Brentford form (all competitions):
D
W
W
L
W
D
Southampton Premier League form:
L
L
L
L
W
L
Southampton form (all competitions):
W
W
L
L
W
L
Team News
Brentford will be without the services of Pontus Jansson and Frank Onyeka due to respective hamstring and thigh injuries, while Shandon Baptiste is doubtful with a groin problem.
Aaron Hickey returned to the matchday squad last time out and watched on from the substitutes' bench after recovering from an ankle injury, and the Scotsman could be selected to start on Saturday at the expense of either Mads Roerslev or Kristoffer Ajer depending on whether Frank chooses to operate with a four or five-man defence.
The likes of Vitaly Janelt, Yoane Wissa, Kevin Schade and Keane Lewis-Potter will all be pushing to start, while top scorer Ivan Toney - who has netted 13 times in 18 Premier League games so far this season - is set to lead the line.
As for Southampton, Kyle Walker-Peters sustained a hamstring injury in the first half against Newcastle and he will now join Valentino Livramento and Juan Larios on the sidelines, while Moussa Djenepo is doubtful with concussion and will be assessed ahead of kickoff.
Jones was criticised by some Saints supporters for starting with a back five in the second leg on Tuesday with his side trailing the cup tie on aggregate, and it remains to be seen whether he will opt to switch to a back four this weekend.
Deadline-day signings Kamaldeen Sulemana and Paul Onuachu - the former of whom arriving for a club-record fee from Rennes - are both in contention to make their debut, but may begin on the bench.
Brentford possible starting lineup:
Raya; Ajer, Pinnock, Mee; Hickey, Jensen, Norgaard, Janelt, Henry; Mbeumo, Toney
Southampton possible starting lineup:
Bazunu; Bella-Kotchap, Bednarek, Salisu; Bree, Alcaraz, Diallo, Perraud; Ward-Prowse; Mara, Adams
We say: Brentford 2-0 Southampton
Brentford will be regarded as favourites to come away with all three points against Southampton considering the contrasting form of the two teams.