Belonging is a basic human need, with social isolation signaling a threat to biological fitness. Sensitivity to ostracism varies across individuals and the lifespan, peaking in adolescence. Government-imposed restrictions upon social interactions during COVID-19 may therefore be particularly detrimental to young people and those most sensitive to ostracism. Participants (N = 2367; 89.95% female, 11–100 years) from three countries with differing levels of government restrictions (Australia, UK, and USA) were surveyed thrice at three-month intervals (May 2020 – April 2021). Young people, and those living under the tightest government restrictions, reported the worst mental health, with these inequalities in mental health remaining constant throughout the study period. Further dissection of these results revealed that young people high on social rejection sensitivity reported the most mental health problems at the final assessment. These findings help account for the greater impact of enforced social isolation on young people’s mental health, and open novel avenues for intervention.