Sir Alex Ferguson's men have made the trip to Spain without three of their most experienced European campaigners.
Rooney, who has endured a tough start to the season, has been ruled out for three weeks with an ankle injury and Scholes for 10 days with a calf complaint, while Giggs has a hamstring problem.
"Facing Manchester United is always difficult, regardless of whether they have a series of injuries to important players or not," said Mata, whose side hammered Turkish champions Bursaspor 4-0 away from home in their Champions League Group C opener as United drew 0-0 with Rangers.
"However, I think that they have a big enough squad to be able to have a good chance in this game.
"They have some top players, so even though Giggs, Scholes and Rooney have been ruled out they will be adequately replaced. It is always difficult to play against them and those who play will be giving 100%."
Mata, a member of Spain's World Cup-winning squad, is disappointed he will not get the chance to come up against Giggs, one of his boyhood idols.
"Giggs is honestly a player who I have always liked, even when I was little," the 22-year-old added.
"His characteristics and his place as one of the best ever wingers to play in Europe are what draw me to him.
"He is a big absentee, above all because of the experience that he has. Other great players are available though, for example Park (Ji-sung), with the talent to cover for him well.
"In any case, for the good of football I hope Ryan recovers quickly and can continue to play for years to come."
The Spanish side go into the game sitting top of the Primera Division table, ahead of Barcelona and Real Madrid and defying the critics who predicted they would struggle to compete following the loss of David Villa and David Silva in the summer.
"The truth is that we are in good form, above all in terms of confidence," said Mata. "We also have results in our favour as the start of the season is going very well. That helps in these types of games.
"We are facing a top opponent and we are in good form, but that won't come into it tomorrow when we have to go out on to the pitch and give our all every minute.
"We hope that the Mestalla, which hasn't seen a game like this for a while, has a great atmosphere and can lift us to a win."