In a role reversal during the Premier League era, the hosts face their bitter rivals chasing a place in Europe, while the Anfield outfit are well and truly in the title raceManchester United boss David Moyes has described Sunday's clash with rivals Liverpool as "the biggest game in the Premier League".
As in recent seasons, the fixture does not pit two title rivals against one another, although this time around it is the reigning champions who have struggled to keep pace at the top rather than their Merseyside visitors.
Due to Moyes' rocky first season in charge, it could be argued his side will be underdogs at Old Trafford this weekend.
Brendan Rodgers' charges have taken 23 points from a possible 27 since the turn of the year and are in the title reckoning thanks, in part, to the fearsome strike duo of Daniel Sturridge and Luis Suarez, who have helped Liverpool net 73 league goals this season.
While the Reds have not won at Old Trafford in their last six attempts in all competitions, Moyes acknowledged on Friday that United could have their work cut out, even on home turf.
"I think it's the biggest game in the Premier League," he said. "There has been great history between the two clubs over a long period.
"[Winning on Sunday] would be a big boost. It would be an important three points. Their league position suggests they're ahead of us and they possibly do come here as favourites."
While Liverpool require a win to maintain title momentum, three points for the champions would merely serve to keep their faint hopes of Champions League qualification alive.
Indeed, the Europa League looks a more realistic proposition, although even that is not a guarantee in a season that has seen United beaten eight times in the top flight.
They sit five points behind fifth-place Spurs, having played a game less, with Sunday's fixture the first of three vital games in just a fortnight.
On Wednesday, they will seek to turn around a two-goal first-leg deficit against Olympiakos in the Champions League last 16 before hosting rivals Manchester City the following Tuesday.
Rodgers will hope Sturridge can add to his 18 Premier League goals and put a further dent in United's season, but the England international feels the result at Old Trafford is not make or break.
"We have got big games regardless of the Manchester United result," the forward told the club's official website.
"Of course we want to do as well as we can in every single game and get maximum points if we can, but it is important we keep playing the football we do.
"I don't think winning at the weekend is going to change anything in regards to the title race."
Moyes was handed a boost in midweek with Nani's return to training from a hamstring injury, while Rafael [ankle], Javier Hernandez [knee] and Jonny Evans [calf] could all return for Sunday's clash.
Rodgers, too, has been boosted after Lucas Leiva [knee] and Mamadou Sakho [tendon tear] returned to contention following spells on the sidelines.