Following their comprehensive two-nil win against Spurs last month, Southampton will be full of confidence for their trip to London as they seek to become the first team to win at White Hart Lane this season.
Meanwhile George Graham's team will be weakened by the suspension of goalkeeper Neil Sullivan, after the Scottish international was dismissed in the recent win against Newcastle.
Sullivan has been in fine form recently, and his faultless display at Goodison Park last week was a major factor in Spurs collecting a point. The former Wimbledon 'keeper has made a total of 85 stops since his arrival in north London and only Mart Poom, with 90, has pulled off more saves this term.
Nevertheless, it gives Ian Walker an opportunity to re-stake his claim as Tottenham's number one and the 29-year-old will be eager to shine in his first start at White Hart Lane since May.
One man who could wreck Walker's big chance is in-form striker James Beattie who has scored 10 goals in his last 12 games, and odds of 7/1 are on offer on Beattie opening the scoring with his first goal of 2001.
The Saints may hand a full debut to Dan Petrescu, as Glenn Hoddle will be hoping his new signing from Bradford can improve his team's passing accuracy. Southampton's 67% pass completion rate is the third-worst tally in the Premiership and three percentage points lower than Spurs' total.
But on the other hand, Opta's stats dispel the myth that Hoddle's teams have no backbone, as the Saint's tackling ratios suggest. Southampton's tackle success rate of 75% is five percentage points better than Spurs, and these defensive stats make them the third-best tacklers in the Premiership behind Coventry and Manchester United.
Tottenham have been plagued by injuries in recent weeks, with Sol Campbell and Les Ferdinand added to the list of walking wounded when both players were forced to miss the trip to Goodison Park last weekend.
But if these two key figures can return to the team then Spurs may just gain revenge for their defeat at the Dell three weeks ago, with an identical 2-0 margin at odds of 11/2 .
Otherwise, if Saints gain a shock win, they will leapfrog Spurs in the table. Then the chants around White Hart Lane will increase for new owners ENIC to install prodigal son Glenn Hoddle into the managers' hot seat as soon as possible.