While the Saints succumbed by a 1-0 scoreline at Crystal Palace in the Premier League, Brentford suffered the same fate in their Championship meeting against Birmingham City.
Having ended the last campaign on a high, Southampton have been tipped to end the current campaign in the top half of the Premier League table.
While Saturday's setback at Palace will be taken in isolation, it has brought Ralph Hasenhuttl's side back down to earth after a seven-match unbeaten streak.
With one of the more favourable starts to the season, the Saints are now under pressure to quickly get back on track, aware that they can ill-afford to replicate their slow beginning to the last campaign.
On a more positive note, Hasenhuttl will likely be able to add to his squad before the end of the summer transfer window, creating a sense of urgency among some of the fringe players who will be given an opportunity in this match.
The same applies to their opponents on Wednesday evening as Brentford look to overcome the disappointment of missing out on Premier League promotion and handle the potential departures of key players.
Thomas Frank will be the first to acknowledge that his side have come nowhere near to replicating their levels of last season in fixtures against Wycombe Wanderers and Birmingham.
While a hangover was always likely, Frank will be concerned that the Bees will struggle to handle the absence of top goalscorer Ollie Watkins, a sale which could be followed by the exit of Said Benrahma.
Although Brentford's unusual transfer policy has paid off immensely, particularly with regards to profit, Ivan Toney and any future arrivals have big boots to fill in the final third.
Southampton form (all competitions): L
Brentford EFL Cup form: D
Brentford form (all competitions): DL
Hasenhuttl could hand a Southampton debut to Mohammed Salisu, who signed from Real Valladolid in the summer.
Southampton possible starting lineup:
Forster; Valery, Vestergaard, Salisu, Vokins; Tella, Smallbone, Romeu, Djenepo; Long, Obafemi
Brentford possible starting lineup:
Balcombe; Rasmussen, Goode, Pinnock, Thompson; Dasilva, Zamburek, Baptiste; Valencia, Forss, Fosu-Henry
We say: Southampton 2-1 Brentford
Given their upcoming Championship schedule, we do not expect Brentford to be prioritising a lengthy run in this competition. While Southampton will also make alternations to their side, they should have enough quality in their ranks to edge out the Bees, potentially by the odd goal in three.