Abstract Background HIV/AIDS remains a public health concern globally. Comorbidities add to the disease burden among people living with HIV (PLHIV) and may be associated with poorer health-related quality of life. This study aimed to assess the prevalence of comorbidities, health-related quality of life (HRQoL), and associated factors among people living with HIV in Gandaki Province, Nepal. Methods A cross-sectional study was conducted at the antiretroviral therapy (ART) centre of Western Region