Background <p>Acute encephalitis is a serious neurological emergency in children, characterized by altered consciousness and brain dysfunction. Prompt recognition and management are essential to reduce morbidity and mortality.</p> Aims <p>This study aimed to determine the prevalence and identify clinical and paraclinical factors associated with mortality and neurological sequelae among children with acute encephalitis admitted to a pediatric intensive care unit (PICU).</p> Methods <p>A retrospective cohort study was conducted over 17 years (2008–2024) in the PICU of Hédi Chaker University Hospital, Sfax, Tunisia. Cases were defined according to International Encephalitis Consortium criteria.</p> Results <p>Of 2,240 PICU admissions, 58 children (2.6%) met inclusion criteria, representing a mean of 3.4 cases per year over the 17-year study period in this tertiary care PICU. Median age was 5 years; 55.2% were male. Common presentations included seizures (82.8%), altered consciousness (69.0%), and fever (82.8%). Among the 46 patients who underwent MRI, neuroimaging abnormalities were detected in 35 (76.1%). Etiology was identified in 81.0% of cases (47/58). Mortality was 20.7% (12/58), and among the 46 survivors, 9 (19.6%) developed neurological sequelae. On univariate analysis, abnormal movements (<i>p</i> = 0.010) and need for supplemental oxygen (<i>p</i> = 0.027) were significantly associated with sequelae, while age under 1 year, seizures at admission, abnormal CT findings, and requirement for advanced resuscitation measures were associated with mortality.</p> Conclusion <p>Pediatric acute encephalitis carries substantial mortality and morbidity. Early diagnosis, comprehensive etiological investigation, and timely intensive supportive care are essential to improve outcomes. Prevention through immunization and enhanced surveillance should be prioritized.</p>