Three cases of Hantavirus Pulmonary Syndrome have been confirmed, and a fourth is suspected, Southern California Public Radio reported.
The National Park Service put out an alert to doctors and hospitals across the country.
The California Department of Public Health said a man died in the San Francisco area in July and the other death occurred last weekend in Pennsylvania. Both had stayed in Curry Village, a popular place for visitors in Yosemite that offers cabins and tent cabins, as did others confirmed or suspected of having the disease.
"To see a cluster of what right now is three, possibly four cases that are all associated with one location -- not one family but different people in the area -- that's unusual," said Dr. David Wong, head of the National Park Service Department of Public Health epidemiology branch.
The virus is carried by deer mice, a species mostly found at high elevations. People are typically infected from breathing the dried feces of infected mice.
The disease was identified 20 years ago.