Data on COVID-19 convalescent plasma (CCP) safety and efficacy in children and young adults are limited. This single-center prospective, open-label trial evaluates CCP safety, neutralizing antibody kinetics, and outcomes in children and young adults with moderate/severe COVID-19 (April 2020–March 2021). A total of 46 subjects received CCP; 43 were included in the safety analysis (SAS); 7.0% < 2 years old, 2.3% 2–<6, 27.9% 6–<12, 39.5% 12– 19 years old; 28 were included in the antibody kinetic analysis (AbKS); 10.7% < 2 years old, 10.7% 6–<12, 53.8% 12– 19 years old. No adverse events occurred. The median COVID-19 severity score improved (5.0 pre-CCP to 1.0 by day 7; p < 0.001). A rapid increase in the median percentage of inhibition was observed in AbKS (22.5% (13.0%, 41.5%) pre-infusion to 52% (23.7%, 72%) 24 h post-infusion); a similar increase was observed in nine immune-competent subjects (28% (23%, 35%) to 63% (53%, 72%)). The inhibition percentage increased until day 7 and persisted at 21 and 90 days. CCP is well tolerated in children and young adults, providing rapid and robust increased antibodies. CCP should remain a therapeutic option for this population for whom vaccines are not fully available and given that the safety and efficacy of existing monoclonal antibodies and antiviral agents have not been established.