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HIV/AIDS because of its transmission methods has cultural, social and psychiatric impacts on patients especially in Islamic countries. We investigated depression frequency in an Iranian referral center for HIV/AIDS patients. All patients attending the counseling centre of Imam Khomeini Hospital during 2006 and 2007 who agreed to participate were enrolled. Depression was measured by Beck Depression Inventory-II (BDI-II) questionnaire. Patients with score 15 and above were considered depressed. 199 patients (27 female; age 37.9‏ ± 9.5) filled the questionnaire. BDI-II scores 13 and above and 15 and above were detected in 74/1% and 71/7% of patients, respectively. We observed statistically significant relationship between depression (as defined by BDI-II score > 15) and CD4 count, duration of diagnosed seropositivity, history of depression in the patients and his/her family, imprisonment, job status and education level. The relationship between depression and addiction was not statistically significant. The observed frequency of depression in our study (74%) is one of the highest ever reported. we recommend regular psychiatric visits for these patients in Islamic countries.