A day after the Saints succumbed by a 1-0 scoreline at Crystal Palace, Spurs suffered the same fate at home to Everton.
While much of the talk this week has been regarding the return of Gareth Bale, Jose Mourinho and his players have been focused on trying to negotiate their first test in the Europa League qualifying rounds against Lokomotiv Plovdiv.
Despite naming a stronger side than expected, Mourinho watched his side have to overcome a one-goal deficit in Bulgaria to move closer to the group stages.
Their victory has added yet another fixture to a punishing schedule which sees Spurs face away games at the Saints, Leyton Orient and Macedonian side Shkendija in the space of five days.
On paper, the North Londoners are favourites for each contest, but Mourinho needs a reaction from his squad after two disappointing performances since the beginning of the campaign.
Although the Portuguese was critical of his team's fitness after the 1-0 defeat against Everton, their upcoming list of matches should give each member of the group a chance to get up to speed.
As far as Southampton are concerned, Ralph Hasenhuttl has been left perplexed by his team's less-than-inspiring displays during defeats to Crystal Palace and Brentford.
Having ended the last campaign on a high, most people expected the South Coast side to continue their momentum as they bid to break into the top half of the standings.
Despite it being early days, Hasenhuttl quickly needs to witness his side show a greater threat in all areas, not just from last season's top goalscorer Danny Ings.
To add to his frustration, the Austrian has revealed that big-money arrival Mohammed Salisu will not slot into the centre of the backline until the back end of October.
Southampton Premier League form: L
Southampton form (all competitions): LL
Tottenham Hotspur Premier League form: L
Tottenham Hotspur form (all competitions): LW
Having picked up a knock against Brentford, it is unclear whether Nathan Redmond will retain his place on the flank.
Bale and Sergio Reguilon have not been signed in time to make their debuts for Spurs this weekend.
Pierre-Emile Hojbjerg will hope to feature against his former side.
Southampton possible starting lineup:
McCarthy; Walker-Peters, Stephens, Vestergaard, Bertrand; Smallbone, Ward-Prowse, Romeu, Djenepo; Ings, Long
Tottenham Hotspur possible starting lineup:
Lloris; Doherty, Alderweireld, Dier, Davies; Ndombele, Hojbjerg; Moura, Lamela, Son; Kane
We say: Southampton 1-1 Tottenham Hotspur
Given the short turnaround, most Spurs supporters will not necessarily expect much from their side when they take to the pitch this weekend. However, they have the quality within their ranks to claim a share of the spoils against opposition who are not firing on all cylinders.
Watch the Sports Mole Football Shorts prediction for this game below: