This data was collected from a longitudinal study nested within the Entebbe Mother and Baby Study birth cohort in Uganda. Adolescents were enrolled and followed up 6 and 12 months later. Blood samples were collected at each visit for SARS-CoV-2 serology. Malaria exposure was defined using prospectively collected data on clinical malaria (from birth to 10 years), asymptomatic parasitaemia at annual visits, and antibody responses to Plasmodium falciparum merozoite surface protein 2 (PfMSP-2) and apical membrane antigen 1 (PfAMA-1). The primary outcome was SARS-CoV-2 seropositivity, based on spike and nucleocapsid IgG responses, with seropositivity cut-offs derived from pre-pandemic samples. Secondary outcomes, including antibody concentrations and symptomatic PCR-confirmed disease, were explored.