The Argentina defender missed the victories against Burnley and Crystal Palace and is now set for an extended spell on the sidelines. Sources have told ESPN that he is set to be absent for a similar period to his original injury.
"Lisandro Martinez will be out of action for an extended period due to an aggravation of the foot injury he suffered in April," the club said in a statement on Friday.
Despite the injury, Martinez played for United in the following two games against Brighton and Bayern.
But it has now been determined that he needs a period on the sidelines for recovery and rehabilitation. Assessment is ongoing to determine next steps.
"Everyone at Manchester United sends Lisandro our best wishes and looks forward to him coming back as soon as possible," the club said in a statement.
Meanwhile, on-loan full-back Sergio Reguilón is expected to miss the Premier League clash against Palace on Saturday after picking up a hamstring injury against Burnley.
He joins Martinez, Aaron Wan-Bissaka, Luke Shaw, Tyrell Malacia, Kobbie Mainoo and Amad on the sidelines. Jadon Sancho remains unavailable while he trains away from the squad while Christian Eriksen and Scott McTominay both missed the Carabao Cup victory over Palace on Tuesday because of illness.