OBJECTIVE: Disease containment of COVID-19 has necessitated widespread social isolation. We aimed to establish what is known about how loneliness and disease containment measures impact on the mental health in children and adolescents. METHOD: For this rapid review, we searched MEDLINE, PsycInfo, and Web of Science for articles published between January 1, 1946, and March 29, 2020. Of the articles, 20% were double screened using predefined criteria, and 20% of data was double extracted for quality assurance. RESULTS: A total of 83 articles (80 studies) met inclusion criteria. Of these, 63 studies reported on the impact of social isolation and loneliness on the mental health of previously healthy children and adolescents (n = 51,576; mean age 15.3 years). In all, 61 studies were observational, 18 were longitudinal, and 43 were cross-sectional studies assessing self-reported loneliness in healthy children and adolescents. One of these studies was a retrospective investigation after a pandemic. Two studies evaluated interventions. Studies had a high risk of bias, although longitudinal studies were of better methodological quality. Social isolation and loneliness increased the risk of depression, and possibly anxiety at the time at which loneliness was measured and between 0.25 and 9 years later. Duration of loneliness was more strongly correlated with mental health symptoms than intensity of loneliness. CONCLUSION: Children and adolescents are probably more likely to experience high rates of depression and most likely anxiety during and after enforced isolation ends. This may increase as enforced isolation continues. Clinical services should offer preventive support and early intervention where possible and be prepared for an increase in mental health problems.