This dataset contains longitudinal serological data from a study nested within the POPVAC B randomised, double-blind, placebo-controlled trial conducted among school-aged children in Uganda. It includes participant demographics, malaria infection status, and SARS-CoV-2 antibody measurements (spike and nucleocapsid IgG) collected at multiple timepoints before and after COVID-19 vaccination. Data capture exposure to intermittent preventive treatment with dihydroartemisinin–piperaquine or placebo, as well as COVID-19 vaccination status and timing. The dataset supports analyses of SARS-CoV-2 seroprevalence, antibody responses, and fold changes in relation to malaria chemoprevention and vaccination in a malaria-endemic setting.