The Spaniards face the Barclays Premier League leaders in a vital game at the Etihad Stadium after losing their opening two Champions League Group A matches to Bayern Munich and Napoli.
City, also anxious to register their first victory in the competition, have demonstrated their formidable attacking ability this term by scoring 27 goals in eight domestic league games and Lopez expects a tough evening.
The 29-year-old Spain international said: "We are mindful of the fact we are playing against the leaders of the English league, a top side.
"But, with respect, you would expect them to create more chances on their own patch than we will manage to create.
"But at this level we have got to show we are up to it and can cope with this situation.
"We will treat the opponents with respect but we will come here with desire and determination to do well and give a good account of ourselves."
Villarreal, who finished fourth in La Liga last term, have struggled this season and are a lowly 13th at home after a goalless draw at Getafe on Saturday.
They also have a number of injury problems with forwards Marco Ruben and Nilmar, midfielders Javier Camunas and Marcos Senna and defender Angel Lopez all failing to make the trip.
Coach Juan Carlos Garrido hopes adversity will bring the best out of the Yellow Submarine.
Garrido said: "When you find yourselves in difficult situations like this, that is when you find out what characters you have got amongst your squad.
"We are determined to come here and do our best, work hard and give a good account of ourselves.
"Out of criticism comes a good test of character.
"I am convinced the guys will show pride and desire for the cause.
"What is important is we show a much better face of Villarreal than we have this season.
"We know we are a better and it is a case of demonstrating that tomorrow."
Ahead of the game Garrido, club president Fernando Roig and four players in Giuseppe Rossi, Jonathan De Guzman, Wakaso Mubarak and Jose Catala will visit Francis House Hospice in Didsbury, where they will spend time and give gifts to children and young adults with life-threatening conditions.