Unna, an 18-year-old killer whale at SeaWorld in San Antonio, Texas, died Monday from a rare fungal infection, park officials announced.
For months, Unna had been battling a resistant strain of a fungus called Candida, which is found in wild cetaceans. A necropsy will be performed to determine the official cause of death, SeaWorld said in a statement.
All killer whale shows were canceled at the park in Unna's memory.
"This is a difficult time for the SeaWorld team and all of Unna’s many fans, and we thank you for your thoughts and well wishes," park managers said.
Unna, born Dec. 27, 1996, had been put on what the park described as a "novel" treatment of medications as they tried to keep the infection from spreading to her kidneys. Killer whales in the wild have an average age of about 50 years.
Unna's death was the latest bad news for the park.
Stella, a female beluga whale, died in November after experiencing gastrointestinal problems, and in July, a premature beluga calf also died.
The chain of marine-themed parks have been grappling with continued fallout from the anti-captivity documentary Blackfish and trying to say relevant against newer, flashier competitors.
SeaWorld has also been facing greater regulatory challenges, including at its flagship park in San Diego, where the California Coastal Commission gave the green light for a $100 million expansion of its killer whale habitats, but banned any breeding of captive orcas.
SeaWorld has also announced that it will ditch its famous killer whale show in San Diego after 2016 and instead launch an "all-new orca experience" in 2017. The new program will be focused more on the "natural" setting, environment, and behaviors of the whale, while also sending a "strong conservation message."