Martinez was forced off during Man United's crushing 3-1 defeat at Arsenal earlier this month.
He's played six games in all competitions this season, but will now face a spell on the sidelines.
Lisandro Martinez comes off against Arsenal.
A club statement read: "Lisandro Martinez will be out of action for an extended period due to an aggravation of the foot injury he suffered in April.
"The Argentinian defender experienced the setback in our Premier League game against Arsenal earlier this month.
"Martinez bravely continued playing for the following two games against Brighton & Hove Albion and Bayern Munich.
"But it has now been determined that he needs a period on the sidelines for recovery and rehabilitation. Assessment is ongoing to decide next steps.
"Everyone at Manchester United sends Lisandro our best wishes and looks forward to him coming back as soon as possible."
The Argentina international will be unavailable for selection on Saturday when the Red Devils resume their Premier League campaign at home to Crystal Palace.
His injury will also see him miss big games in the Champions League against Galatasaray and Copenhagen as well as league fixtures against the likes of Manchester City and Newcastle United.
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