The buffalo was rescued from flooding in Bear Creek Park on Thursday.
VIDEO: Bison rescued from flood waters in Bear Creek Park
While rescue workers and veterinarians alike expected Buffy's condition to improve, officials at Texas A&M determined she had kidney failure.
Sadly, Buffy died Saturday, according to Harris County Precinct 3 Commissioner Steve Radack's office.
Buffy was the last living descendent of a pair of bison brought to Bear Creek Park 30 years ago.
Radack says she will be missed by park visitors and by the county workers who looked after her.