The Red Devils exited the Champions League in controversial circumstances in midweek, with Nani's second-leg red card the main talking point of their last-16 defeat to Real Madrid.
And the 29-year-old expects a “very difficult” game at Old Trafford with United looking to bounce back from that disappointment.
He told reporters: “This is a game for us to show character and a game to react after this one [in Bucharest]. It is going to be very difficult, like always.
“It is going to be one of our biggest challenges of the season, especially playing them at this moment.
“When you go out of the biggest competition in that way, it must be disappointing but they will be more motivated because of that.”Chelsea find themselves 19 points short of their next opponents in the Premier League, and the Serbia international says his side must work extra hard during the run-in to make up for that deficit.
“One thing is more important than any other, to play every game as a final, as a team, to try to win every game,” he continued.
“The supporters didn’t expect us to be in this situation this year. We have to be realistic with our situation and be honest. The gap means we didn’t do well in the season.”