Weir, who was looking forward to celebrating the 10th anniversary of his only Major win at Augusta next month, walked off the Bay Hill course after going four-over through 11 holes.
Playing on a career money earnings exemption after three barren injury plagued seasons, Weir had begun to show signs of turning his game around by making the cut at Bay Hill.
The Canadian lefty had made the cut in just five PGA Tour events over the last three years, three of those coming this season where his best finish was a tie for 50th at Pebble Beach.
"I'm feeling closer," Weir said after his opening round on Thursday. "It's not easy but it's part of the game.
"I want to compete and that makes the hard work easier. I still love the game, still enjoy practicing and being out there."
Weir had been scheduled to play the Houston Open next week in his final competitive tune-up before the year's first Major.
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