We hypothesized that higher levels of self-compassion among people living with HIV (PLWH) would be related to lower levels of loneliness, which in turn would be associated with better psychological well-being (lower levels of depression and negative affect and higher positive affect). 106 PLWH completed an online survey that measured demographic variables, self-compassion, loneliness, and psychological well-being. Mediation analyses revealed that loneliness mediated the relationship between self-compassion and depression and negative affect, but not positive affect. These findings indicate that encouraging self-compassion may have a positive effect on psychological well-being among people living with HIV by reducing loneliness.