The current study examines if perceived negative changes due to COVID-19 are related to adolescent loneliness, stress and depressive symptoms and whether friendship factors (online friend communication, friend support) serve a protective role in these associations. In total, 993 adolescents (M[subscript age] = 16.09, SD = 1.24) from ethnically diverse backgrounds (49% White, 18% Asian/Asian-American, 14% Latinx, 9% Black/African-American, 10% Other) in the United States completed an online survey. Adolescents who perceived more negative changes due to COVID-19 reported more loneliness, stress and depressive symptoms. For loneliness and stress, these associations were qualified by interactions with the friendship factors. Among adolescents with low online friend communication, as perceived negative changes increased, loneliness also increased. At high levels of friend communication, there was no link between negative COVID-19 changes and loneliness. Friend communication and support may protect adolescents from well-being problems stemming from the negative changes in their life due to COVID-19.