The 31-year-old Spaniard has not featured for the Gunners since the 6-0 Champions League win over Ludogorets on October 19.
It had been hoped the playmaker, who scored twice during Arsenal’s impressive opening to the new campaign, would be able to recover without going under the knife.
However, the club announced in a statement on Thursday afternoon that he would need to undergo an operation.
“Santi Cazorla is travelling to Sweden early next week to undergo surgery to his right ankle,” a statement on www.arsenal.com said. “The club’s medical team and specialists have decided that surgery is required to the plantaris tendon in the Spain international’s right foot.
“The problem has not progressed during a rehabilitation programme following the injury during the home match with Ludogorets on October 19.
“We expect Santi’s full recovery to take approximately three months. Everyone at the club will be working hard with Santi to make sure he’s back on the pitch as soon as possible.”
Sheffield United could have leading scorer Leon Clarke back for their home game against Nottingham Forest.
St Johnstone midfielder Murray Davidson is determined to use their derby exploits as a springboard to rid them of inconsistency.
Lincoln will once again be without skipper Luke Waterfall for Saturday's League Two derby clash with Grimsby.
Leeds boss Paul Heckingbottom is expected to choose from an unchanged squad for the home game against Sheffield Wednesday.
Derek Fazackerley will take the Oxford helm on the 56th day of his caretaker stint in Saturday's match against Peterborough.