Human infections with Japanese encephalitis virus (JEV) are a leading cause of viral encephalitis. After a bite from an infected mosquito, JEV replicates in peripheral monocytes and produces a systemic viremia. JEV can enter the brain via break-down of the blood brain barrier and infect neurons, triggering cell death and inflammation (encephalitis). In encephalitic human cases, approximately 1/3 develop lethal encephalitis, 1/3 develop permanent neurological sequalae, and 1/3 fully recover. The molecular events that define these three different outcomes is not known. We have established state-of-the-art adult immunocompetent mouse models of JEV in physical containment 3 laboratories that recapitulate this spectrum of disease. Mice that succumbed to disease had robust JEV infection of neurons, and H&E detectable brain lesions consistent with those seen in post-mortem human brains, including neuron degeneration, gliosis, meningitis, leukocyte infiltrates, microgliosis, and haemorrhage. Mice that lost >5% body weight and recovered had prolonged histopathological lesions and immune responses, indicating these mice survived a non-lethal encephalitis. Mice that didn’t lose at least 5% body weight had undetectable changes in the brain, indicative of an asymptomatic viremia. Herein we present data from histology and immunohistochemistry, RNA-seq, and single cell spatial transcriptomics (CosMx) to identify in high-resolution the spatiotemporal immunological and pathological events that distinguish lethal versus non-lethal flavivirus encephalitis. Our findings highlight a subtype of astrocytes as key players in survival.