Six patients with Powassan Virus encephalitis were identified, and all had documented tick exposures between the months of March and October in New England. The age at diagnosis ranged from 14 months to 11 years, and 83% were female. All patients presented with fever and confusion, and the majority also presented with seizures and headache. Cerebrospinal fluid showed mixed lymphocytic and neutrophilic pleocytosis with mean WBC 137 (range 62-221), normal glucose, and slightly elevated protein. Brain MRI revealed leptomeningeal enhancement in 5 patients, T2/FLAIR hyperintensity in the bilateral basal ganglia and deep grey nuclei in all patients, as well as varying degrees of hyperintensity in the cerebral white matter. Spine MRI was abnormal in only one patient on presentation, and one additional patient developed cord and nerve root enhancement over time. All patients were treated with high dose steroids, and 5 were treated with IVIG. The median length of initial hospitalization was 18.5 days, and most patients were discharged to rehabilitation centers. All patients had lasting neurologic sequelae including behavioral problems, ADHD, dystonia, movement disorders, learning problems, anxiety, OCD, sleep disturbances, and seizures.