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Background: The COVID-19 public health crisis has created abrupt and unparalleled disruptions to the daily lives of children and adolescents across the world, placing them at significant risk for developing symptoms of anxiety and depression., Method: The current study used two data collection periods to determine which types of COVID-19-related stressors were associated with the greatest risk of anxiety and depression symptoms in a community sample of children and adolescents in the United States (U.S.) from May-August 2020 (T1) to February-April 2021 (T2). Seventy-nine youth (ages 10-17; M = 13.41, SD = 2.10; 54.4% female) completed a battery of online standardized questionnaires about COVID-19 stress and psychiatric symptoms at T1 and 56 of these also participated at T2., Results: The majority of children and adolescents reported experiencing the COVID-19-related stressors in multiple domains including daily routines, interpersonal relationships, education, finances, and health. A substantial proportion of the sample reported clinical levels of depression and anxiety symptoms at both T1 and T2. Multiple linear regression analyses revealed that, controlling for T1 anxiety and depression symptoms, T2 interpersonal stressors were significantly associated with elevated depression and anxiety scores at T2., Conclusions: The findings highlight the salience of social connection for children and adolescents, and may also underscore the risk associated with lockdown restrictions, social distancing, and school closures during the pandemic., (© 2022 Association for Child and Adolescent Mental Health.)