Health-related quality of life (HRQoL) is one of the most important indicators in assessing the health and well-being of HIV-positive patients. The present study investigated the HRQoL of HIV patients referred to Abadan’s Voluntary Counseling and Testing (VCT) center in 2019. In this cross-sectional study, a total of 134 HIV+ patients referred to Abadan’s VCT center were selected through convenience sampling. Demographic information was collected through a researcher-made checklist; the patients’ status and health information were collected through electronic medical records of HIV+ patients and their records at the VCT center. The HRQoL index was assessed using the World Health Organization (WHOQOL-BREF) questionnaire. Data analysis was carried out using simple and multiple linear regression as well as a t -test in SPSS software. A P value < 0.05 was considered as the significance level in all tests. The mean of the HRQoL in all the participating patients was 56.42 ± 22.66 . The highest and lowest mean scores of HRQoL domains were related to social relationships ( 57.53 ± 24.73 ) and environmental health ( 53.68 ± 19.07 ). There was a positive significant relationship between the marital status, residency, years of education, duration of infection, transmission route, and antiretroviral (ARV) therapy with the score of the HRQoL. The results showed a moderate score for the mean HRQoL and its domains. The present study revealed the necessity of improving HIV+ patients’ living conditions, employment status, health education, and mental health care.