Arsenal were surprisingly beaten in the League Cup Final by Birmingham City, knocked out of the Champions League by Barcelona and missed a chance to close on United in the Premier League when they drew 0-0 at home with Sunderland.
Manager Arsene Wenger, bristling with fury at the red card for Robin van Persie that he felt contributed to their 3-1 loss in the Nou Camp, must refocus his energy as he seeks his first trophy since winning the FA Cup in 2005.
With United also standing in the way of the Premier League title and the two teams due to meet at Emirates Stadium next month, Saturday's game is a chance to gain a psychological advantage.
Arsenal have not won at Old Trafford since 2006, losing there in the league, Champions League and FA Cup, a 4-0 thrashing in 2008.
They are likely to be without Cesc Fabregas after the captain aggravated a hamstring strain against Barcelona and will definitely miss first-choice goalkeeper Wojciech Szczesny after he dislocated a finger.
With Theo Walcott also likely to miss out and Andrey Arshavin struggling for form, it looks a tough task for Arsenal, also beaten 1-0 at Old Trafford in December.
"We've we got to pick ourselves up, we have to go there on Saturday and get a win," midfielder Jack Wilshere said. "We are still in two competitions and we want a trophy."
United have also experienced a mini-slump with back-to-back league defeats at Chelsea and Liverpool but they remain a formidable force at home, where they have won 13 and drawn one of 14 league games this season.
The record 11-times cup winners will be without winger Nani on Saturday after he suffered a cut shin in the 3-1 Liverpool defeat but Sir Alex Ferguson's team plans are likely to remain a secret if the manager maintains a media blackout he imposed in the wake of the two league defeats.
Reading are the only remaining club from outside the Premier League in the competition after the Championship side beat Everton at Goodison Park to reach the last eight for the second successive season.
They face a tough task to go any further, however, as they visit Manchester City on Sunday.
City have probably given up any realistic hope of winning the league but the Cup offers a great opportunity for their first silverware since 1976.
After waiting 48 years for a cup success Birmingham are now eyeing two in one season as they host Bolton Wanderers on Saturday.
Birmingham climbed out of the relegation zone with a 1-1 draw at Everton on Wednesday and manager Alex McLeish faces a difficult juggling act with a series of crunch games against relegation rivals on the horizon.
Two more clubs taking a break from the relegation fight are Stoke City and West Ham United, who meet in the Midlands on Sunday.
Stoke, who have never reached the final, lost to Chelsea in the quarter-finals last
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