Abstract: Objective Our objective was to describe clinical characteristics and course of pediatric bupropion ingestions requiring extracorporeal membrane oxygenation (ECMO) life support. Desgin The study included a retrospective cohort of patients ≤18 years of age reported to a regional poison control (PC) system covering three states in the upper Midwest United States. All bupropion exposures ≤18 years of age, coded as receiving ECMO to treat toxicity, were included. Clinical presentation and management including ECMO are presented as descriptive statistics. Results During the study period, 4,951 bupropion exposures were reported; 1,145 (23.1%) were children. Nine patients were coded as undergoing ECMO; four (44.4%) were ≤18 years of age (median 16, range 14–17). All were treated with venoarterial ECMO. The median time from ingestion to presentation was 2.25 hours (range: 1–3.5). Median first systolic blood pressure and pulse were 100 mm Hg (range: 70–124) and 119.5 (range: 70–175). The median time from ingestion to ECMO was 17.63 hours (range: 7.25–33.75); median number of vasopressors was 2.5 (range: 2–3). All experienced multiple seizures, ventricular dysrhythmias, and hypotension. Three of four sustained cardiac arrest. All but one required transfer to an ECMO-capable facility for definitive care. Three patients survived with full neurologic recovery; one died. Conclusion Pediatric bupropion cases requiring ECMO were rare in this study. Time to initiation and duration of EMCO suggest that the variable onset of hemodynamic instability may delay ECMO initiation. It is incumbent on PCs and medical toxicologists to educate prescribers and pediatricians about bupropion's potential lethality and to consider early transfer to an ECMO center.