After coming out on top in an end-to-end tussle at Old Trafford in September, Tottenham can reinforce their own Champions League ambitions with a second successive win over the Premier League leaders who beat West Ham United 1-0 on Wednesday to reach the FA Cup fourth round.
That would be a remarkable achievement in itself given they have not won a home fixture against United, who are seven points clear at the top of the table, since 2001, 11 years after they last won both the home and away league matches.
It would be an indication of the direction in which the club is heading under Portuguese manager Andre Villas-Boas who has begun to win around sceptical supporters after replacing the enormously popular Harry Redknapp in the close season.
After a short-lived and underwhelming spell at Chelsea, Villas-Boas was hired to bring modern European thinking to the Tottenham helm where Redknapp's more traditional methods had led them to a fourth-place finish the previous season.
They sold Luka Modric, arguably their most influential player, but Villas-Boas has kept them in top-four contention and was rewarded with the manager of the month award in December.
His list of achievements include bringing the best out of Gareth Bale, successfully converting Jermain Defoe into a lone striker and skilfully managing a depleted squad.
To complete a league double over United would add another feather to his cap given Redknapp did not manage a single win against the Manchester club in any competition in his four years with the club.
Last weekend's draw with Redknapp's current club Queens Park Rangers, however, gave fans reason for concern.
A 1-1 draw with Wolverhampton Wanderers at a similar stage last season was the start of a prolonged dip in form that allowed Arsenal to come from 10 points behind to leapfrog them into third place.
"It is in everyone's minds because it has happened before," said Tottenham's midfielder Scott Parker, who could return to the starting lineup after coming off the bench in their last six league games following a prolonged injury layoff.
"As a team and as a squad we need to maintain our performances. Maybe what happened in the past will stand us in good stead. I just think we can learn from two years ago and last year and stay strong."
A win would also give Tottenham the opportunity to close the gap on third-placed Chelsea who have to negotiate a tricky home game against inconsistent Arsenal on Sunday to maintain their own fading title challenge.
Chelsea fans are struggling to warm to interim manager Rafa Benitez whose side were held to a shock 2-2 league draw by Southampton on Wednesday to continue the Spaniard's uphill battle to convince the club's supporters that he can be trusted.
Chelsea, who sit six points behind second-placed Manchester City, take on an Arsenal side capable of being both brilliant and blunt.
Languishing in sixth place and 21 points behind the leaders, Arsenal, who booked their place in the FA Cup fourth round with a last-gasp win over Swansea on Wednesday, need a win to perk up their own challenge for a Champions League spot.
Laurent Koscielny may return to the heart of the Arsenal defence after serving a one-match suspension following his sending-off against Manchester City who entertain Fulham on Saturday.
The champions will be able to call on captain Vincent Kompany who had his own red card from the Arsenal match rescinded by the FA following widespread condemnation of the decision to send him off for a well-timed sliding tackle.
City striker Sergio Aguero could also feature having returned to training following a hamstring injury.
Liverpool can soothe the wounds inflicted by local rivals Manchester United last weekend with victory at home to Norwich City while Newcastle United, who have lost four of their last six league matches, host second-bottom Reading.
France striker Loic Remy could make his debut for bottom club Queens Park Rangers at West Ham United on Saturday after completing his move from Olympique Marseille.
In the weekend's other fixtures, Swansea host Stoke City, Wigan Athletic entertain Sunderland and West Bromwich Albion face Aston Villa on Saturday. Everton travel to Southampton on Monday
- Sports & Recreation
- West Ham United
- Champions League
- Harry Redknapp