The Germany international was injured during Arsenal’s Premier League victory at Sunderland last weekend and is now a doubt for the rest of the season and the season-ending European Championship.
Mertesacker, who has 79 caps for Germany, had reconstruction surgery on his ankle before joining Arsenal from Werder Bremen in August.
“Unfortunately he has had surgery and we have lost him for a while,” Wenger told reporters.
“How long I don’t know. He had reconstruction of his ligaments. So it will be long term.”
Arsenal, who suffered a demoralising 4-0 defeat to AC Milan in the Champions League on Wednesday, will also be without defender Laurent Koscielny when they play Sunderland for the second time in eight days in the FA Cup on Saturday.
Koscielny was forced off with a knee injury in the first half of their midweek humbling in the San Siro, but should be fit to return next week.
“He had a scan yesterday and the news is quite good. He will be out for hopefully around a week,” Wenger added.
“He will miss the Sunderland game but he should be back for next week.”
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