Bupropion inhibits the reuptake of norepinephrine and dopamine and is an effective therapy for both depression and smoking cessation. It is structurally similar to amphetamine, and despite it’s good safety profile, it is increasingly being abused to obtain non-medical psychoactive effects and can also be fatal in overdose. We present a fatal case of bupropion toxicity with cardiogenic shock refractory to Impella placement. A 32-year-old male with a history of depression and polysubstance abuse presented to the ED after consuming an unknown quantity of bupropion tablets in a suicide attempt. He was initially alert and hemodynamically stable, though quickly became somnolent and had a generalized tonic-clonic seizure. He was intubated, and supportive care measures were initiated, including activated charcoal and whole bowel irrigation. Over the next 12 hours the patient had progressive vasopressor-dependent hypotension, metabolic acidosis, acute renal failure, and prolonged QRS and QT intervals. He was on a sodium bicarbonate infusion as well as escalating doses of norepinephrine, epinephrine, and vasopressin. An echocardiogram demonstrated severe dilated cardiomyopathy with an EF of 20%. An impella was placed, followed by initiation of lipid emulsion infusion. Despite these therapies, the patient died 36 hours after admission. Bupropion overdose most commonly results in seizures, though it also has cardiotoxic potential. The cardiotoxicity is likely related to its effect on myocyte gap junctions, which are critical to forming a coordinated cardiac contraction. This leads to a sodium bicarbonate-resistant cardiogenic shock, unlike that seen in overdose from medications like TCA’s which effect sodium channels. To our knowledge, this is the first reported case of Impella insertion for cardiac support in bupropion toxicity. In similar cases, it may be beneficial to pursue early transfer to a facility that can administer ECMO. There have been good outcomes with VA-ECMO for refractory cardiogenic shock in poisoned patients, including those with bupropion toxicity. Those with cardiovascular failure related to poisoning may particularly benefit from ECMO, given that the toxicity is likely to resolve if the patient can be adequately supported until drug clearance.