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To identify etiologies of altered mental status in pediatric patients presenting to the emergency department (ED) and to characterize the yield of diagnostic testing in these patients.Retrospective chart review of children aged 1-17 years presenting to a pediatric tertiary care ED between December 31, 2013 and December 31, 2014 with a chief complaint or International Classification of Disease, Ninth Edition code of altered mental status. The primary outcome was the etiology, defined as “immediate diagnosis” if the etiology was known in triage, “definitely established” if established by physical examination and abnormal laboratory results, imaging, or electrocardiogram findings, “probable” if the etiology was highly suspected in the ED but not confirmed with positive test results, or “unknown.” The secondary outcome was testing utilization and contribution to the diagnosis.Three hundred thirty-six eligible subjects were identified; mean age of 9 years (±6 years). The etiology of altered mental status was immediately established in 114 subjects (34%, 95% CI 29, 39). Among the remaining eligible subjects (N = 222), a definite or probable cause of altered mental status was identified in 82% (N = 182, 95% CI 76, 86) of cases and the etiology remained “unknown” in 18% (N = 40, 95% CI 14, 24). Only 10% of diagnostic tests performed were abnormal and contributed to a diagnosis. The median number of diagnostic tests per patient was 6 (IQR 3, 8).Etiologies of altered mental status in children varied widely and often an underlying diagnosis was not found. Broad diagnostic testing was commonly performed although the overall yield was low.