David Moyes' side currently sit ninth in their domestic league following back-to-back defeats against Everton and Newcastle.
However, their place in the latter stages of Europe's top competition has already been confirmed and the veteran Romanian is expecting a tough match at Old Trafford.
"Even though they are not playing well, these are two different competitions and you can't really compare them," Lucescu said at a press conference.
"In the Premier League, the English teams know each other and the teams they are playing, but with the Champions League it is a totally different situation.
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"I watched both defeats, against Everton and Newcastle. When they were playing Everton it was David Moyes' former team so they were playing with special enthusiasm and motivation, but when they played Newcastle it was like they had lost their spark a bit.
"The result of the game does depend on some small things, though. For example, if they got a penalty for the handball against Newcastle, it could have been completely different.
"Every manager knows their squad back to front and each individual player, and each manager has his own style. Some prefer to rotate to keep the squad fresh and some prefer to keep the same team.
"In David Moyes' case he likes to rotate his team but the squad is very strong and therefore the quality of the players doesn't diminish."