The Dutchman has failed to recover from a groin injury he sustained whilst on international duty and was forced to miss the Gunners Premier League win over Manchester City on the weekend.
Wenger is confident going into the match despite being without the predatory instincts of van Persie.
The confidence is highlighted by a great return to form by Emanuel Adebayor with a double against City.
“I believe it is always good to win before you go to another big game and it lifts the confidence and belief of the team a bit more,” said Wenger in a press conference on Monday.
“We are on a good run so we feel we are consistent and it is a good basis to go into a Champions League game.
“You know in Europe you want to focus, and we have learned something this season. The squad has learned to treat every game with a lot of respect and with a lot of commitment.
“We have learned as well from 2006 and the semi-final that with Villarreal you face a tough game. And that is why we prepare ourselves to just be at our best.”