Safety not assured
Both teams are on 40 points with three games to play but, while that is widely regarded as a safety marker, they are still looking over their shoulders.
The drop zone is eight points back but the next three below them - Burnley, Leeds and Everton - have at least one game in hand and it is possible, if still unlikely, that all three could break the 40-point barrier.
Brentford's remaining fixtures after this match are away to Everton and at home to Leeds and that puts something on this match, although it is arguable that both teams might be happy with a point. The draw is available at 3.613/5.
Brentford boss Thomas Frank might make changes after last week's 3-0 defeat at Manchester United, only their second loss in their last eight games.
A return to a back four looks likely, which would allow Yoane Wissa to line up in a front three with Ivan Toney and Bryan Mbeumo.
The midfield could get a shake-up, with Mathias Jansen and Josh Dasilva possible starters after coming on in the second half at United.
Frank Onyeka and Mathias Jorgensen are out for the season and Ethan Pinnock, Sergi Canos and Saman Ghoddos have been struggling with injuries.
Saints on a poor run
Southampton have dropped below Brentford on goal difference after a poor run of late-season form.
Last week they held a half-time lead against Crystal Palace through Oriol Romeu's early goal but eventually went down 2-1 as Wilfried Zaha grabbed a stoppage-time winner.
Ralph Hasenhuttl's side play Liverpool next at home and will be keen to shore up their position by taking something from this match.
Stuart Armstrong, Mohamed Elyounoussi and Armando Broja were second-half substitutes against Palace and could be given the chance to start here.
Romain Perraud is set to continue at left-back in place of Valentino Livramento, who will be out for a long time with a serious knee injury.
Brentford lost 4-1 in the reverse fixture at St Mary's on January 11, which was the start of a terrible run where they picked up just one point in eight matches.
Their season has turned around over the last eight, however, with five wins and a draw giving them 16 points and putting them fourth in the form table.
Part of the turnaround is explained by an easier run of games. Having lost mainly to top-eight sides since the Southampton defeat, Brentford's revival started with a 3-1 win away to rock-bottom Norwich, although with confidence restored they have gone on to beat Chelsea (4-1 away) and West Ham (2-0 home).
Given that Southampton are 15th, it is worth noting the differences in Brentford's record in 2022. Their figures against the top eight are W2 D1 L6 and against the teams currently below 11th they are W4 D1 L1 - the only defeat being against Southampton.
In addition, their home record against those lower-placed sides this season is W4 D1 L1 and their last two home matches are in that category, with Leeds to follow Southampton.
With the standard of opposition a key factor in Brentford's performance, this looks a good time to play Southampton.
When they met at St Mary's, Hasenhuttl's side had already started a turnaround of their own that would eventually lead to a record of W5 D4 L1 in 10 games (Brentford were the fourth opponent in that run).
Since then, the Saints have slumped again with a record of W1 D2 L6. Their only shutout in that run helped them to a 1-0 home win over Arsenal, but they have conceded at least two goals in seven of the other eight.
In their case, the poor run is harder to explain in terms of the standard of the opposition. Among the teams to have beaten them are Aston Villa, Watford, Burnley and Crystal Palace, who are all around or below them in the table.
Southampton have shown they are capable of much better form this season but there is not much sign of it at the moment and Brentford are a clear pick based on recent form and their overall home record at this level.
Brentford to win at 2.265/4 is the selection and it could be worth combining star striker Toney as anytime goalscorer with a home win in a Bet Builder at 3.14 as he has scored in five of his last 10 starts for the Bees.
Toney's recent goals have been central to Brentford's resurgence and he has figured on the scoresheet in six of the last eight games where they have scored.
Both teams are in the middle rank for goals with a 54% rate of games with over 2.5 goals, although the figure has shifted upwards in the last eight games (both 62%) with Brentford's surge and Southampton's slump.
Southampton's away figure is further up at 71% over 2.5 goals but Brentford are on the low side at home (41%).
That lower figure is explained by the success of Brentford's tightly controlled structure at home.
When they are on form, Frank's side tend towards lower figures. Three of their first four at home had under 2.5 goals during their good start to the season and likewise their last five at home have gone that way in their recent revival.
Under 2.5 goals could be the call at 2.01/1.
A low-scoring Brentford win feels likely. Three of their six home wins have been 2-0 (the other have been 2-1 twice and 1-0) and that score is available at 13.012/1.
Brentford have kept a clean sheet in each of their last three Premier League home games, and could become just the fourth side to record a shutout in four in a row at home this term after Arsenal, Liverpool and Manchester City. A Brentford win to nil is 3.8514/5.