We spoke to Football London's Tottenham correspondent Alasdair Gold to get the Lilywhites' view ahead of tonight's Premier League clash at Wembley...
Derby defeat to Arsenal, at risk in the Champions League but still in contention in the Premier League, what’s the current mood like at Spurs?
The players will definitely be down after Sunday's defeat but the overall mood in the camp shouldn't take too much of a hit.
Spurs have been through the wringer this season with their stadium delays, injuries and a lack of signings to bolster the squad, but they've maintained their momentum on the whole.
The biggest headache for Mauricio Pochettino has been juggling his starting XI for matches every three days, but he's doing a decent job of keeping most of his squad happy with the minutes they're getting.
Spurs are six points ahead of where they were at this stage last year and their fate is in their own hands in the Champions League, so it's not doom and gloom in the camp despite Sunday's setback.
Spurs were unable to withstand Arsenal’s second-half onslaught at the Emirates, are there defensive frailties to be targeted for Saints?
It's all about tiredness. Spurs have had a match every couple of days for a few weeks now and injuries have meant that the core of the team have had to play almost every game.
They tired in the second half on Sunday and the Saints will be hoping the same happens again on Wednesday night.
At the back, it's likely to be Toby Alderweireld and Juan Foyth in the centre with Jan Vertonghen suspended. Foyth is a young player with a lot of potential, but he's also made a few mistakes in his first four Premier League outings and Southampton will no doubt target him.
Who has been Spurs’s surprise performer this term?
There's only contender here - Moussa Sissoko. The Frenchman has turned around most Tottenham fans' opinions about him and he's been one of the team's most important players in recent months.
His technique is occasionally a bit inconsistent but he's been providing a vital function for the team in the middle. Pochettino says there's nobody better in his team when it comes to transitions, switching the team from defence to attack, and that Sissoko brings balance to the team.
He's started every game recently so there's some doubt over whether he'll start again at Wembley on Wednesday night and if he doesn't Spurs will miss his workrate.
Who will the key men be for Spurs on Wednesday night? Are changes likely to made from the North London Derby?
Pochettino will make plenty of changes to bring in much-needed fresh legs. Harry Winks, Lucas Moura and Toby Alderweireld will likely come in, along with fit again full-backs Danny Rose and Kieran Trippier. That's almost half the team changed already.
In terms of key men, Harry Kane of course is always a threat even if he's one of those who has been starting every game and must be tiring.
Lucas Moura will also be looking to show what he can do again, having fallen slightly from the high standards the Brazilian set earlier in the season.
Spurs of course have game-changers in Christian Eriksen, Heung-Min Son and Dele Alli but one or two of that trio could find themselves on the bench.
What sort of game are you expecting?
If you'd asked me this a week ago I'd have said this should be a comfortable victory for Tottenham.
However, a week is a long time in football. Since then the Saints achieved that battling draw against United and have a new manager on the way, with the players no doubt looking to impress, while having an extra day's rest.
Tottenham have had that north London derby defeat since and are starting to look tired mentally and physically.
It should be a proper battle on the Wembley turf and both teams will have to dig deep to come away with the points.