Murphy, 25, will be sidelined for up to seven weeks after sustaining the injury in training and his setback will force head coach Uwe Rosler to draft in cover in time for the new season’s opening game at home against Burnley on August 8.
Leeds released central midfielder Rudy Austin at the end of last season and a hunt for a new midfielder looks likely.
“We lost Rodolph Austin and now we lost Luke Murphy. That answers the question,” head coach Uwe Rosler told the Yorkshire Evening Post.
“He twisted his knee without anyone around him,” Rosler added. “It was a very unlucky situation and the last minute of the training session.
“He’s already gone for a small procedure on his knee. I don’t think we’ll have him back ready to play in the first game against Burnley. We’ll be thinking between four and seven weeks.”