Sustained-release bupropion is commonly used for the symptomatic relief of depressive disorders and as an adjuvant in smoking cessation therapy. The frequency of adverse reactions with bupropion has been estimated to be more than 1%. Hypersensitivity reactions to bupropion are fairly common and include rare cases of serum sickness-like reaction. Here we report a case of bupropion hydrochloride induced serum sickness-like reaction. Complete resolution of symptoms was achieved on discontinuing bupropion and instituting therapy with glucocorticoid and a non-steroidal antiinflammatory drug.We report this case to notify clinicians of potential serious multisystem complications that can occur with sustained-release bupropion therapy.