COVID-19 has had far-reaching effects on people’s lives, with evidence of a disproportionate impact on marginalized groups. Given existing health disparities and research on minority stress, COVID-19 may have uniquely impacted psychological well-being among sexual minorities. In an online survey of adults in the U.S. (N = 1,007) conducted in April 2020, we examined differences between sexual minority and heterosexual participants in psychological well-being, social distancing, computer-mediated communication, and COVID-19-related worry and experiences. Sexual minorities reported lower thriving and greater psychological distress, social distancing, computer-mediated communication, and COVID-19 worry and experiences than heterosexual participants. Social distancing and distress were positively correlated among sexual minorities and more frequent computer-mediated communication predicted greater thriving across groups. Path analyses showed sexual minorities’ poorer psychological well-being was mediated by their greater COVID-19 worry and social distancing, in particular. These findings shed light on the distinct impact of COVID-19 on sexual minorities.