Background Nodding syndrome (NS), is an unexplained form of epilepsy which leads to stunted growth, cognitive decline, and a characteristic nodding of the head. Current data about its impact on households in Uganda is scarce. Therefore, this study aims to assess the economic burden of the persistent morbidity of NS on caregivers in affected households in Northern Uganda. Methods A cross-sectional cost-of-care study was conducted from January 2019 to February 2019 in Lakwela village-Northern Uganda in 14 households, who are members of a communitybased organization (CBO) established in the village with the support of a Japanese research team, (Uganda-Japan Nodding Syndrome Network). Data was collected through questionnaires. Both direct (medical and non-medical) and indirect (informal care) costs of caregiving were assessed. Indirect costs were valued using the human-capital method as loss of production. Results Direct costs constituted a higher proportion of costs for NS households, accounting for on average 7.7% of household expenditure. The annual weighted mean cost per NS patient was estimated at 27.6 USD (26.4 USD direct costs, 96.2% and 1.2 USD indirect cost,