Liverpool are expected to be at full strength for the match on Merseyside, while league leaders United hope to welcome back captain Nemanja Vidic for the clash.
Building up to English football's most anticipated fixture Sports Mole takes a look at three key encounters from the Premier League era.
1993/94: Liverpool 3-3 Man Utd After goals from Steve Bruce, Ryan Giggs and Denis Irwin had given champions United a seemingly insurmountable 3-0 lead, a Nigel Clough double dragged the hosts back into contention. The stage was set for headline-grabbing Neil Ruddock to earn the Merseyside club an improbable point with a courageous header, before he rubbed his head in disbelief in front of the travelling Mancunian support.
1994/95: Liverpool 2-0 Man Utd A year later, Manchester United were chasing a third consecutive league title when they visited their fiercest rivals. With only two months of the season remaining, United knew that they had to win to keep pace with Kenny Dalglish's Blackburn Rovers. Goals from Jamie Redknapp and a Steve Bruce own goal seriously deflated the Old Trafford side for the title run-in, and when Blackburn won the league at Anfield two months later the red half of Merseyside celebrated as if it were one of their own triumphs.
2006/07: Liverpool 0-1 Man Utd Playing badly and winning is the mark of champions, they say, and Manchester United would have struggled to have played any worse than they did on this crisp, spring afternoon at Anfield. After taking a battering for 90 minutes, Sir Alex Ferguson's side snatched the three points when John O'Shea was on hand to hit home Cristiano Ronaldo's free kick after Pepe Reina had spilled. The Red Devils didn't look back as they won the league by six points. The match is also remembered for Paul Scholes taking a swing at Xabi Alonso. And missing.