Studies on health-related quality of life (HRQoL) inequalities according to sexual orientation are scarce. The aim of this study was to assess HRQoL inequalities between lesbian, gay, and bisexual (LGB) people and heterosexuals in the 2011 Barcelona population, to describe the extent to which sociodemographic characteristics, health-related behaviors, and chronic conditions could explain such inequalities, and to understand if they are sexual orientation inequities.