Omicron variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a health concern for both unvaccinated and vaccinated individuals against coronavirus disease 2019 (COVID-19). To date, the humoral immune response following vaccination and natural infection remains uncharacterized in children ages 17 years and younger. To address this concern, we performed clinical and immunological analyses of IgM and IgG antibody responses to SARS-CoV-2 Omicron BA.2.38 infection in 64 pediatric patients. COVID-19 symptom severity decreased with age in pediatric patients, from 70.8% (17/24) in patients 0-2 years of age to 50% (6/12) and 50% (14/28) in patients 3-5 years and 6-17 years of age, respectively. Furthermore, fewer patients experienced symptoms when vaccinated with the CoronaVac or BBIBP-CorV vaccine (50%, 13/ 26) than unvaccinated patients (71%, 22/31). Using a protein array, we found that the Omicron BA.2.38 infection induced antibody responses to other Omicron variants (Omicron BA.1-BA.5), which increased with vaccination. Notably, non-Omicron and Omicron variants showed distinct serotypes. Altogether, our results provide insight into the clinical and immunological characteristics of pediatric patients with COVID-19 Omicron BA.2.38 who have and have not been vaccinated against COVID-19. These data may help develop more effective diagnostic tests and vaccines in the future.