United haven't won at Stamford Bridge since 2002 and saw their title hopes extinguished by Carlo Ancelotti's side at Old Trafford last April, when Didier Drogba's bullet strike swung the championship firmly in the direction of the London club.
The Red Devils will be keen for revenge while Chelsea will hope their big-money signing Fernando Torres can cause Nemanja Vidic more misery, similar to what the Spaniard achieved during his time at Liverpool.
A fascinating contest is in store - but how do you think the game will go? Leave us your comments below with your suggested scoreline.
Castrol Football's experts have forecast the outcome and we'll reveal their answer on Tuesday before the showdown.