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To assess the frequency, interventions, and outcomes of children presenting with traumatic brain injury or infectious encephalopathy in low-resource settings.Prospective study.Four hospitals in Sub-Saharan Africa.Children age 1 day to 17 years old evaluated at the hospital with traumatic brain injury or infectious encephalopathy.None.We evaluated the frequency and outcomes of children presenting consecutively over 4 weeks to any hospital department with traumatic brain injury or infectious encephalopathy. Pediatric Cerebral Performance Category score was assessed pre morbidity and at hospital discharge. Overall, 130 children were studied (58 [45%] had traumatic brain injury) from hospitals in Ethiopia (n = 51), Kenya (n = 50), Rwanda (n = 20), and Ghana (n = 7). Forty-six percent had no prehospital care, and 64% required interhospital transport over 18 km (1–521 km). On comparing traumatic brain injury with infectious encephalopathy, there was no difference in presentation with altered mental state (80% vs 82%), but a greater proportion of traumatic brain injury cases had loss of consciousness (80% vs 53%; p = 0.004). Traumatic brain injury patients were older (median [range], 120 mo [6–204 mo] vs 13 mo [0.3–204 mo]), p value of less than 0.001, and more likely male (73% vs 51%), p value of less than 0.01. In 78% of infectious encephalopathy cases, cause was unknown. More infectious encephalopathy cases had a seizure (69% vs 12%; p < 0.001). In regard to outcome, infectious encephalopathy versus traumatic brain injury: hospital lengths of stay were longer for infectious encephalopathy (8 d [2–30 d] vs 4 d [1–36 d]; p = 0.003), discharge rate to home, or for inpatient rehabilitation, or death differed between infectious encephalopathy (85%, 1%, and 13%) and traumatic brain injury (79%, 12%, and 1%), respectively, p value equals to 0.044. There was no difference in the proportion of children surviving with normal or mild disability (73% traumatic brain injury vs 79% infectious encephalopathy; p = 0.526).The epidemiology and outcomes of pediatric traumatic brain injury and infectious encephalopathy varied by center and disease. To improve outcomes of these conditions in low-resource setting, focus should be on neurocritical care protocols for pre-hospital, hospital, and rehabilitative care.