Bupropion, a first-line pharmacological treatment for nicotine addiction, is a reuptake inhibitor of dopamine and norepinephrine. Dopaminergic effects of bupropion may cause or worsen psychosis (Kumar et al., 2011; Munoli et al., 2014). We reported a case with schizoaffective disorder (SD), who presented with bupropion-induced acute psychotic episode. A 36-year-old man diagnosed to have SD, who has been on remission with risperidone 3 mg/d, Valproic Acid (VA) 1000 mg/d for four years. Family physician prescribed bupropion 300 mg/d two months ago for smoking cessation. The patient reported that the symptoms appeared on the 15th day of bupropion use. During psychiatric examination; he seemed deteriorated and presented logorrhea, elevated mood, disorganized behavior and speech, paranoid-grandiose delusions, ideas of reference, delusions of persecution, auditoryvisual hallucinations and insomnia. No impairment in orientation and memory functions was observed. PANSS score was 132/210. He has been initially treated with a combination of risperidone 3 mg/d and VA 1000 mg/d for three weeks and on the 3rd week, only his psychomotor agitation was alleviated. An increase in the dosage of risperidone to 6 mg/d caused exacerbation in extrapyramidal symptoms and as a result, biperidene 2-4-6 mg/d was added to his treatment. After dosage titration, his psychotic symptoms worsened and he did not respond to treatment. Risperidone was discontinued gradually and clozapine was added to VA. As soon as clozapine dose was titrated up to 250 mg/d, the patient’s symptoms and PANSS (58/210) scores showed significant improvement. Psychosis as a side effect of bupropion is rare in patients without a pre-existing history of psychosis (Javelot et al., 2009, 2010). Appearance of psychotic symptoms after bupropion use may be associated with inhibition of dopamine reuptake (Javelot et al., 2009, 2010; Kumar et al., 2011) especially in patients with history of psychotic symptoms. Treatment of bupropion-induced psychosis may be difficult and achieving remission may take some months. Healthcare professionals should check for any psychotic symptoms or disease before prescribing bupropion for smoking cessation.