Background: Limited data are available on childhood encephalitis. Our study aimed to increase insight on clinical presentation, etiology, and clinical outcome of children with severe encephalitis in the Netherlands. Methods: We identified patients through the Dutch Pediatric Intensive Care Evaluation database and included children diagnosed with encephalitis <18 years of age admitted to 1 of the 8 pediatric intensive care units (PICU) in the Netherlands between January 2003 and December 2013. We analyzed demographic characteristics, clinical symptoms, neurologic imaging, etiology, treatment and mortality. Results: We included 121 children with a median age of 4.6 years (IQR 1.3–9.8). The most frequently described clinical features were headache (82.1%), decreased consciousness (79.8%) and seizures (69.8%). In 44.6% of the children, no causative agent was identified. Viral- and immune-mediated encephalitis were diagnosed in 33.1% and 10.7% of the patients. A herpes simplex virus infection (13.2%) was mainly seen in children <5 years of age, median age, 1.73 years (IQR 0.77–5.01), while immune-mediated encephalitis mostly affected older children, median age of 10.4 years (IQR, 3.72–14.18). An age of ≥ 5 years at initial presentation was associated with a lower mortality (OR 0.2 [CI 0.08–0.78]). The detection of a bacterial (OR 9.4 [CI 2.18–40.46]) or viral (OR 3.7 [CI 1.16–11.73]) pathogen was associated with a higher mortality. Conclusions: In almost half of the Dutch children presenting with severe encephalitis, a causative pathogen could not be identified, underlining the need for enhancement of microbiologic diagnostics. The detection of a bacterial or viral pathogen was associated with a higher mortality.