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The aim of this study was to assess the quality of life (QOL) and the severity of depression in people living with HIV/AIDS (PLWHA) and investigate its correlates. This was a cross-sectional study on 700 PLWHA in India. World Health Organization QOL HIV (WHOQOL HIV-BREF) and Patient Health Questionnaire-9 (PHQ-9) were used to assess QOL and depression in PLWHA, respectively. The study population was divided into five groups on the basis of Cluster of Differentiation 4 (CD4) count as follows: Group A [< 50 cells/μL], Group B [50-199 cells/μL], Group C [200-349 cells/μL], Group D [350-499 cells/μL], and Group E [>500 cells/μL]. The lowest mean scores were noted under Group A [< 50 cells/μL] in physical and psychological domains and the highest mean scores were noted under Group E [> 500 cells/μL] in physical and environment domains. PHQ9 scores negatively correlated with QOL domains and the correlation was statistically significant (p < 0.001) with the highest negative correlation was found in relation to the psychological domain (r = -0.739). The PHQ9 score in those who do not have opportunistic illnesses (7.23 ± 6.14) was lower in comparison to those who had opportunistic illnesses (9.81 ± 6.40) and the difference was statistically significant (p < 0.001). We observed that there was almost a chronological increase in the individual QOL domain score and a decrease in the PHQ9 score with an increase in CD4 count. Our result supports the implementation of routine screening for depression in antiretroviral therapy centers and multidisciplinary interventions to improve outcomes among depressed PLWHA., (Copyright: © 2021 Permanyer.)