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Acute encephalitis is relatively uncommon but potentially devastating. The prognosis varies from complete recovery to severe sequelae or death. The diagnosis is difficult to establish and the etiology often remains unclear. Furthermore, the long-term prognosis of acute encephalitis in children is poorly described and prognostic markers in the acute phase are lacking. In this thesis, the aim was to characterize acute encephalitis in childhood in regard to etiology, clinical presentation and long-term outcome. Another aim was to study biomarkers in CSF of children with TBE and to identify markers predicting the long-term outcome. Methods: We retrospectively studied the medical records of all children with acute encephalitis at Astrid Lindgren Children´s hospital in Stockholm during 2000–2004 (study I). This cohort was followed-up 3-8 years later using 2 questionnaires grading persisting symptoms and every day functioning. Seventy-one children were eligible for the follow-up (study II). In study III, 55 children with TBE in 2004-2008 were evaluated 2-7 years later. Two questionnaires were used grading persisting symptoms and executive functioning in everyday life. General cognitive ability was also investigated in a subgroup, using WISC-IV. In study IV, cytokines, chemokines and markers of neuronal damage were analyzed in CSF samples from 37 children with TBE in 2004-2010, using a multiplex assay. Results: The etiology of childhood encephalitis was dominated by TBE, EV, VZV, influenza virus and RSV, but remained unknown in 52% of cases. Fever and encephalopathy were present in a majority of the children, seizures or focal neurological deficits were seen in 40%. EEG-examinations were pathological in 90%, and 55% of the children with acute encephalitis had pleocytosis. There were no mortalities, but 60% of the children had persisting symptoms at the time of discharge. In the long-term follow-up, persisting symptoms were reported by 54%, both in children with and without