Former Crewe Alexandra forward Clayton, who had a trial with Sunderland ahead of the 2014-15 campaign, was hurt in Bolton's goalless draw with Ipswich Town on Saturday.
And the north-west club confirmed on Thursday that he is facing a lengthy lay-off.
A message on Bolton's official Twitter account read: "Max Clayton is set to be out of action for 6 months after surgery on the anterior cruciate ligament in his right knee."
Clayton, 19, missed a large chunk of the previous campaign after breaking an ankle.
He tweeted: "Devastating news to be out for the rest of the season ... but will come back stronger than ever ready for the challenge of next season."
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