Thomas Frank's men overcame Colchester United in midweek after falling short against Liverpool, while the Saints responded to their defeat against Nottingham Forest by sinking Cardiff City in an eight-goal extravaganza.
Match preview
Ending Crystal Palace's Premier League purple patch on the opening weekend was not a sign of things to come for Brentford at Anfield, where Frank's men succumbed to strikes from Luis Diaz and Mohamed Salah either side of the half-time whistle.
There were certainly pleasing aspects of the performance for Frank to reflect on - Brentford's resilient work out of possession restricted Liverpool to few clear-cut first-half chances - and the Bees avoided a cup giant killing in midweek too.
However, only a Keane Lewis-Potter strike on the stroke of the break could see off Colchester United, who were gifted a late opportunity to keep the tie alive from 12 yards, only for stand-in Brentford goalkeeper Hakon Valdimarsson to keep out Jack Payne's penalty.
Before turning their thoughts to a challenging September - where fixtures against Manchester City and Tottenham Hotspur come either side of an EFL Cup contest with Leyton Orient - Brentford go in search of back-to-back Premier League home wins for the first time since November 2023.
The Gtech faithful have every right to expect their side achieving that feat in emphatic fashion, as they have marched to seven straight home wins over newly-promoted Premier League sides, scoring at least twice in each victory in that sequence.
Meanwhile, Southampton have only conceded twice in their first two matches back in the big time, although both of those strikes have condemned Russell Martin's men to painful losses, as Nottingham Forest followed Newcastle United's lead on matchday two.
The St Mary's contest was certainly one of the more forgettable showdowns of the second gameweek, where a solitary Morgan Gibbs-White effort propelled Forest to a deserved victory, but there was nothing boring about Southampton's EFL Cup opener in the Welsh capital.
Indeed, Martin's men and Cardiff City shared an extraordinary eight goals between them, as Martin's men took the lead three times only to be pegged back on three occasions, but injury-time interventions from Cameron Archer and James Bree saw the Saints march on.
Putting their first Premier League points on the board at the third time of asking is now the overriding goal for Southampton, who may be dominating possession like never before, but they could now lose their first three league fixtures of a season without scoring for the first time since 2001-02.
The visitors' head-to-head record against Brentford suggests that such a miserable scenario could come to fruition, as since prevailing 4-1 in their opening Premier League battle, they have failed to earn a single point or score a single goal against the Bees, losing their last three by an aggregate score of 8-0.
Brentford Premier League form:
Brentford form (all competitions):
Southampton Premier League form:
L
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Southampton form (all competitions):
Team News
Yet another week has passed without any clarity on the future of Ivan Toney, who again was not involved in the Liverpool loss and is apparently attracting interest from all of Chelsea, Manchester United and Al-Ahli ahead of Friday's transfer deadline.
However, the Bees have reinforced their attacking ranks themselves with the capture of Gustavo Nunes from Gremio, while Yoane Wissa and Bryan Mbeumo are both well-rested and should spearhead the hosts' charge on Saturday.
Igor Thiago (knee), Rico Henry (knee), Aaron Hickey (thigh) and Josh Dasilva (knee) make up a quartet of guaranteed Brentford absentees, while Valdimarsson's penalty heroics in midweek will not be enough to keep Mark Flekken at bay.
Speaking of goalkeepers, Southampton are pushing to get a £25m deal for Arsenal's Aaron Ramsdale over the line before the transfer window slams shut, and the Englishman would certainly come straight into the first XI if registered in time.
Ramsdale could expect to be Southampton's number one for as long as Gavin Bazunu is out with an Achilles injury - a comeback has been pencilled in for early 2025 - but Alex McCarthy made a number of saves in the loss to Forest and is still a competent option at the top level.
Ross Stewart is still building up his fitness and might not be back in time for the trip to London, but Kamaldeen Sulemana has made a full recovery from an ankle injury and should provide an alternative option in the Saints attack.
Brentford possible starting lineup:
Flekken; Roerslev, Collins, Pinnock, Ajer; Norgaard, Janelt, Jensen; Mbeumo, Wissa, Lewis-Potter
Southampton possible starting lineup:
McCarthy; Stephens, Bednarek, Harwood-Bellis; Sugawara, Fernandes, Smallbone, Downes, Walker-Peters; Brereton Diaz, Archer
We say: Brentford 2-0 Southampton
For all of their periods of plentiful possession, Southampton remain deprived of a killer touch in the final third, whereas Brentford always possess a clinical threat up top when Mbeumo and Wissa are working in tandem.