Health-related quality of life (QOL) has become a high priority of long-term management of HIV-infected individuals. The newly diagnosed HIV cases were assessed to obtain sociodemographic and clinical findings. Eyesenk Personality Questionnaire (EPQ), World Health Organization Quality of Life Brief (WHOQOL-BREF) for HIV-infected patients, and Beck Depression Inventory (BDI) were used to get data regarding personality traits, QOL, and depression scores. A total of 175 patients were included in the study, 128 (73.1%) men and 47 (26.9%) women. Overall 56% of patients screened positive for depression. Presence of depression and high neuroticism score in the personality profile of HIV-infected patients are significantly associated with poorer QOL. High neuroticism score was a strong predictor of poorer QOL in psychological and spiritual domain. Management of HIV-infected patients therefore needs to address these psychological issues. © The Author(s) 2012.