The COVID-19 pandemic led to a worldwide lockdown and school closures, which have placed a substantial mental health burden on children and college students. Through a systematic search of the literature on PubMed and Collabovid of studies published January 2020–July 2021, our findings of five studies on children and 16 studies on college students found that both groups reported feeling more anxious, depressed, fatigued, and distressed than prior to the pandemic. Several risk factors such as living in rural areas, low family socioeconomic status, and being a family member or friend to a healthcare worker were strongly associated with worse mental health outcomes. As schools and researchers discuss future strategies on how to combine on-site teaching with online courses, our results indicate the importance of considering social contacts in students’ mental health to support students at higher risk of social isolation during the COVID-19 pandemic.