The two-time Cy Young Award winner's season will effectively be ended by the second surgery on his shoulder in less than three years while playing under a six-year, $137.5 million contract.
The deal is set to expire at the end of the campaign, likely meaning his career with the Mets is over.
The pitcher missed all of the 2011 season after suffering a similar injury in September 2010.
After reporting to spring training this year, Santana was diagnosed with weakness in his left shoulder. He has not appeared in a spring training game.
Santana was the Mets' opening day starter last year and on June 1 threw the first no-hitter in the history of the franchise. He did so while throwing a career-high 134 pitches.
In his next 10 starts Santana went 3-7 with an ERA of 8.27. The Mets eventually shut him down for the season in August.