Nola, a 41-year-old northern white rhino, died after being treated for a bacterial infection and age-related health issues, the zoo said.
The rhino’s condition had worsened significantly in the last 24 hours, and zoo veterinarians made the decision to euthanize her.
Forty-one years is at the upper end of a white rhino’s life expectancy.
Nola was one of only four northern white rhinos in the world, according to the zoo. The remaining three are in the Ol Pejeta Conservancy in Kenya.
The northern white rhino is a subspecies of white rhino. The northern subspecies is believed to be extinct in the wild, according to the World Wildlife Fund, while the “near threatened” southern white rhino population is growing in sanctuaries.
Rhinos are the second largest land mammal after the elephant.
The San Diego Zoo is working to save the northern white rhino subspecies through the collection of genetic material and the development of assisted reproductive technologies.
The zoo tweeted about Nola’s death Sunday: “We’re devastated by the loss of Nola.”