Maki, a ring-tailed lemur, was discovered missing on Thursday morning when zoo keepers prepared to open up to the public.
“We understand that lemurs are adorable animals, but Maki is a highly endangered animal that requires special care," said Dr Jason Watters, zoo executive vice president of animal behaviour and wellness.
"We are asking the public for help in his return".
Dr Watters added: “As one of our oldest lemurs, Maki requires a specialized diet. Of the 19 lemurs here...he has exceeded median life expectancy of 16.7 years, but is also one of the slowest, and we believe, likely, the easiest to catch," Watters said.
Investigators found evidence of a forced entry to the lemur enclosure and processed the scene for evidence.
They're seeking tips from the public and have circulated a photo of a ring-tailed lemur to help with their enquiries.
Lemurs are native to Madagascar and listed as an endangered species.
San Francisco Zoo & Gardens outdoor lemur habitat is considered one of the largest in the US and houses seven different species of the animal, according to the zoo's website.
"Guests can see the lemurs from several vantage points: from across a surrounding pond, looking eye to eye at lemurs in the trees or gazing down below from an elevated boardwalk," the website says.
It is the second time in the space of two years that a lemur has been stolen from a California zoo.
In 2018 the oldest ring-tailed lemur in captivity in North America was bundled out Santa Ana Zoo late at night.
The culprit, Aquinas Kasbar, of Newport Beach, was sentenced to 90 days in prison and ordered to pay the zoo $8,486 in costs.
Associated Press contributed to this report.
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