Background: Young people who experience higher levels of social support from their schools and families have been shown to be less likely to develop symptoms of negative mental health outcomes such as depression and anxiety. This raises questions concerning how young people's stress and psychological changes due to the COVID-19 pandemic as well as social support during this time have affected their overall mental health. The aim of this study was to assess the association between sources of parental- and school-level social support and youth perceptions of COVID-19-related emotional impact on mental health among early adolescent girls and boys in Appalachia. Methods: Using linear regression, we analyzed the first and third wave of survey data from the larger parent study (Young Mountaineer Health Study) cohort, collected in 20 middle schools throughout West Virginia in the fall of 2020 and fall of 2021 (N = 1349, mean age: 11.5, response rate: 80.7%). Results: Approximately half of participants reported knowing someone that had been sick with COVID-19. Those experiencing higher levels of perceived COVID-19-related emotional impact reported greater levels of depression, anxiety, and anger. Both parental and school-level social support were associated with better mental health outcomes. Conclusions: Early adolescent perceptions of COVID-19-related emotional impact were associated with depression, anxiety, and anger and moderated by social support at home and in school among 11-12-year-old youth in Appalachia.