The Dutchman, who has scored 13 goals since January, is still suffering from a knee injury he picked up when he netted in the 2-1 League Cup final defeat to Birmingham on Sunday.
The in-form striker, who also scored in the first leg against Barcelona, underwent a scan and it seems as though he has no chance of recovering in time to face the Primera Division leaders.
The loss of Van Persie comes as a bitter blow to Wenger, who is also without winger Theo Walcott due to an ankle injury he picked up in the 2-1 Premier League win against Stoke last week.
In some good news for Gunners fans, Barcelona target and Arsenal captain Cesc Fabregas is expected to be fit for the game after missing the League Cup final with a minor hamstring injury.
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