This study examines the relationship between family rejection and moderate to severe psychological distress during COVID-19 among LGBTQ university students. Data were obtained from a national cross-sectional electronic survey of LGBTQ university students ( = 565) collected in the summer of 2020. Hierarchical logistic regression models were used to examine the predictive association between increased family rejection and moderate to severe psychological distress. Respondents who reported increased rejection were more than twice as likely to report moderate to severe psychological distress, with social isolation and LGBTQ identity concealment being significant covariate predictors in the model. These results demonstrate the importance of public health, medical, mental health, and higher education stakeholders understanding the significance of LGBTQ-identity related family rejection when addressing the mental health and well-being of LGBTQ young people.