Objective: To analyze whether sexual orientation affects the quality of life of people living with HIV/Aids (PLWHA). Method: A crosssectional analytical study was carried out with 146 PLWHA in Teresina, capital city of the state of Piauí, in 2013, by means of the WHOQOL-HIV-bref. Descriptive analysis and multiple linear regression were used for data analysis. Results: There was a prevalence of men (63.7%), non-heterosexual (57.0%), aged between 19 and 39 years (89%). Of the total, 75.5% mentioned presence of negative feelings, such as fear and anxiety, and 38% reported have suffered stigma. With regard to the dimensions investigated, the most affected were "environment" and "level of independence". Non-heterosexual orientation was negatively associated with quality of life in almost all dimensions. Conclusion: Living with HIV/Aids and having a non-heterosexual orientation have a negative impact on quality of life.