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Objectives: AIDS is among chronic disorders that severely affects the individuals’ physical and mental health. Considering the importance of spirituality in counteracting the stress arising from chronic diseases and accepting the disease, our study aimed to determine the relationship between spirituality and mental health in HIV-positive patients who referred to the Behavioral Disorders Center in Tabriz, Iran. Materials and Methods: This descriptive analytic cross-sectional research was conducted on 81 HIV-positive patients referred to behavioral disorders center of Tabriz, Iran in 2017 using the census method. The instruments used in this study included socio-demographic characteristics questionnaire, Parsian and Dunning’s spirituality questionnaire, and General Health Questionnaire-28 (GHQ-28) . Data analysis was carried out through independent t test, one-way ANOVA, Pearson correlation coefficient, and multiple linear regressions. Results: The mean (SD) of the overall mental health score was 36.0 (16.4) (range: 0-84). Two-thirds of the patients suffered from mental health disorder; mean (SD) of overall spirituality score in people suffering from positive HIV was 89.0 (15.3) (range: 29-116). The relationship between the total score of spirituality and overall mental health and its sub-domains was significant (P<0.05). Self-awareness was the only mental health predictor. Conclusions: A considerable percentage of people with HIV suffer from mental health disorders. Regarding the positive relationship between spirituality and all mental health sub-domains, strengthening spirituality can lead to the promotion of mental health in these patients.