Full Text Article. Also available at: https://academic.oup.com/tropej/article/64/5/426/4682722Background: Malaria and acute bacterial meningitis (ABM) are the leading infectious causes of febrile encephalopathy in malaria endemic settings. The clinical distinction of the two conditions is complicated by overlap in clinical features. Objective: To determine the clinical predictors for malaria, ABM and treatment outcome in febrile children aged 2 months to 12 years with altered mentation at two tertiary hospitals in Northwestern Tanzania. Methods: Prospective study of 103 children to document demographic data and physical examination findings, such as level of consciousness and meningeal irritations. Laboratory results for cerebrospinal fluid, hemoglobin, malaria and HIV were also evaluated. Results: Age>60 months and hemoglobin 5 g/dl were independent predictors of malaria; (p¼0.013 and 0.004, respectively). HIV infection was the only predictor of meningitis, p¼0.037, and mortality was high if the diagnosis was unconfirmed. Conclusions: Children with febrile encephalitic are more likely to have malaria than ABM if they have severe anemia.