Everglades virus (EVEV), an alphavirus in the Venezuelan equine encephalitis (VEE) serocomplex, circulates among rodents and vector mosquitoes and infects humans, causing a febrile disease sometimes accompanied by neurologic manifestations. EVEV circulates near metropolitan Miami, which indicates the potential for substantial human disease, should outbreaks arise. We characterized EVEV infection of cotton rats in South Florida, USA, to validate their role in enzootic transmission. To evaluate whether the viremia induced in cotton rat populations regulates EVEV distribution, we also infected rats from a non-EVEV-endemic area. Viremia levels developed in rats from both localities that exceeded the threshold for infection of the vector. Most animals survived infection with no signs of illness, despite virus invasion of the brain and the development of mild encephalitis. Understanding the mechanisms by which EVEV-infected cotton rats resist clinical disease may be useful in developing VEE therapeutics for equines and humans.