The orange and white tabby named Meow, who was between 2 and 5 years old, was taken to the Santa Fe Animal Shelter & Humane Society last month after his 87-year-old owner could no longer take care of him.
The shelter put Meow on a diet and posted all his weigh-ins on a Facebook page that got national attention.
Meow had lost 2 pounds and was doing well when he began having breathing problems Wednesday, shelter Director Mary Martin said Monday.
Meow underwent a battery of tests, including X-rays and a cardiac ultrasound, and was put on oxygen.
Despite the shelter's best efforts, Meow died on Saturday.
"It was a shock and a horror for all of us," Martin told The Associated Press through tears. "We all fell in love with him."
She said people across the country contacted the shelter after Meow's story made national news, with many telling her he inspired them to put their pets and themselves on a diet.
It's not clear how Meow gained so much weight, but Martin said it was likely a simple combination of a high-calorie diet and inactivity.
Adult cats typically weigh between seven and 12 pounds.
