Defeat for Chelsea, 11 points behind United in the Premier League title race with eight games to play, would put manager Carlo Ancelotti under huge pressure less than a year after he led the team to a league and FA Cup double.
The Italian knows his future is on a knife-edge after an uneven season and recent history between the two clubs suggests that the Champions League tie, which concludes at Old Trafford next Tuesday, will be decided by the slimmest of margins.
Chelsea go into the match with a good record at home against United. They are unbeaten in their last 10 matches against Sir Alex Ferguson's men, including last month's Premier League game when they came from behind to win 2-1 with a goal from David Luiz and a Frank Lampard penalty.
Chelsea's front men, however, have been lacklustre with Didier Drogba, Nicolas Anelka, Salomon Kalou and Fernando Torres scoring just three goals in their last nine matches.
Torres, two months after his £50 million move from Liverpool, is still looking for his first goal for Chelsea after eight appearances, and might start on the bench.
Chelsea drew 1-1 at Stoke City on Saturday, though they played better than the result suggested, and Ancelotti is looking forward to Wednesday's game.
"The condition of the players is good psychologically and physically. We don't have any problems and we are ready to play United. We have the confidence to do our best and win," he said.
"We know that United have the same opinion. It will be a very exciting game, a very tough game. We know everything about Manchester United and they know everything about us. Whoever deserves to win, will win."
Saturday's victory at West Ham left United seven points clear of Arsenal at the top of the table.
"Those things happen in your career and it's important how you react, and we've kicked on with our performances. We're now going into Wednesday's game with a lot of confidence - and so we should."
