"The patient died of complications related to severe thrombocytopenia," a condition related to a low number of platelets in the blood, the US Centers for Disease Control and Prevention said.
"Although Zika virus-associated deaths are rare, the first identified death in Puerto Rico highlights the possibility of severe cases, as well as the need for continued outreach to raise health care providers' awareness of complications that might lead to severe disease or death."
The CDC investigated a total of 6,157 suspected Zika cases in Puerto Rico between November 1, 2015 and April 14, 2016, according to the CDC report.
The CDC has warned of a potential explosion of Zika cases in Puerto Rico, possibly reaching into the hundreds of thousands.
Zika is known to cause the brain defect microcephaly, and is blamed for a recent surge in cases of malformed babies in Brazil.