Not only will the boss want United to bounce back from Tuesday's Champions League disappointment but the memories of the last time the sides met in the FA Cup, in the 2007 final, are likely to further fuel Sir Alex's insatiable hunger for success.
"I felt we were very unlucky to lose the 2007 final," he told Inside United recently. "Didier Drogba scored in [almost] the last minute of extra time after we had a very strong penalty shout turned down.
"I think Ryan Giggs may have forced the ball over the line as well for a goal that wasn’t given. That was tough to take, but that’s football – you win some, you lose some."
The boss has often talked about the lack of FA Cup winners' medals in his current squad. Indeed, only Ryan Giggs, Paul Scholes and Darren Fletcher have won the competition for United.
The arrival of Robin van Persie in the summer added another FA Cup winner to the list, although Robin's success, in the 2005 final, came against the team he now hopes to help win the trophy for a record 12th time.
"Don't remind me of that game!" Sir Alex quipped. "We annihilated Arsenal, it was like the Alamo. They had one shot and we had something like 23 shots on target."
At the end of the 90 minutes, though, scores remained 0-0 and it was still goalless after extra time. Paul Scholes was the only man to miss his penalty in the shootout, handing Arsenal (and a 21-year-old van Persie) the cup.