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Comorbidity of psoriasis and psychiatric disorders is a common situation and psoriasis patients use more antidepressant medications than the general population. Exacerbation of psoriasis with antidepressant therapy has been rarely reported in previous studies. Herein, we report a case of psoriasis triggered by bupropion treatment in a patient with major depression. A 33-year-old female had moderate psoriasis plaques on the knees and legs, controlled with emollients and topical corticosteroids in childhood from eight to eleven years of age. Her last psoriasis attack had been several years ago, and no lesions has been present since then. Patient’s second episode of depression has emerged seven weeks ago. She was reluctant to use venlafaxine She began taking şuoxetine 20-60 mg per day (two months), and after she began reboxetine 4-8 mg per day (one month) her depression did not respond to above listed treatments. She dropped these drugs and she did not use any drug for two weeks due to her reluctancy. She began to take sustained release form of bupropion 150 mg. Four days after starting this treatment she developed plaques on her scalp, chest and arms, where she had such reactions for the first time. Upon withdrawal of bupropion, her lesion improved dramatically in the following period of four days. After then, she restarted taking venlafaxine 75-150 mg per day. She kept on recovering under this treatment without any exacerbation of psoriasis. Benefit of antidepressants is obvious in patients with psoriasis accompanying psychiatric disorders. However clinicians should be aware of the potential adverse effects of bupropion to aggravate pre-existing psoriasis.