The Belgian Pro League champions were beaten 3-1 at Old Trafford last week, with Memphis Depay netting a double and Marouane Fellaini sealing the win after Preud'homme's men had taken the lead.
Brugge will face United in the second leg on Wednesday but Preud'homme is pessimistic over his side's chances against Louis van Gaal's men.
"Miracles happen sometimes, but they are two goals in front and they are a very professional team," Preud'homme told reporters.
"To get a miracle, you need to be perfect and you need the other to not play at his best potential. We have a lot of players out, too.
"If we want to have a chance, we have to be perfect. It will be very difficult, but let's pray.
"This United team can live with pressure.
"They have it each day, each minute in each game. When you see this team playing, they play on their quality, against Tottenham, against Newcastle, against us. They keep doing the same.
"I don't think they'll have more pressure if we score, but it's important for our confidence if we score."
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