Bupropion, sold under the brand name Wellbutrin among others, is an atypical antidepressant primarily used to treat major depressive disorder and to support smoking cessation. It is also popular as an add-on medication in the cases of "incomplete response" to the first-line selective serotonin reuptake inhibitor (SSRI) antidepressant. Bupropion has several features that distinguish it from other antidepressants: it does not usually cause sexual dysfunction; it is not associated with weight gain and sleepiness, and it is more effective than SSRIs at improving symptoms of hypersomnia and fatigue. Bupropion, particularly the immediate release formulation, carries a higher risk of seizure than many other antidepressants and caution is recommended in patients with a history of seizure disorder.

Common adverse effects of bupropion with the greatest difference from placebo are dry mouth, nausea, constipation, insomnia, anxiety, tremor, and excessive sweating. Raised blood pressure is notable. Rare but serious side effects include seizure, liver toxicity, psychosis, and risk of overdose. Bupropion use during pregnancy may be associated with increased odds of congenital heart defects.

Bupropion acts as a norepinephrine–dopamine reuptake inhibitor and a nicotinic receptor antagonist. However, its effects on dopamine are weak. Chemically, bupropion is an aminoketone that belongs to the class of substituted cathinones and more generally that of substituted amphetamines and substituted phenethylamines.

Bupropion was invented by Nariman Mehta, who worked at Burroughs Wellcome, in 1969. It was first approved for medical use in the United States in 1985. Bupropion was originally called by the generic name amfebutamone, before being renamed in 2000. In 2020, it was the eighteenth most commonly prescribed medication in the United States, with more than 28 million prescriptions. It is on the World Health Organization's List of Essential Medicines.