Encephalitis lethargica (EL), also known as the ‘European Sleeping Sickness’, emerged in Europe around 1916, with Sweden reporting the highest global incidence rate in 1921. This study investigates regional variations in EL incidence across Sweden between 1920 and 1930, with a particular focus on the major outbreak in 1921. Using data from Public Health in Sweden, incidence rates were calculated for all Swedish regions, revealing a disproportionate concentration of cases in central and northern areas, especially in the parish of Vilhelmina in Västerbotten. To contextualize this outbreak, monthly disease data from the Annual Reports of the Chief Provincial Doctor in Västerbotten were analysed to compare the local disease panorama. Notably, preceding the first EL cases in Vilhelmina, influenza/H1N1 and mumps were frequently reported. Although the aetiology of EL remains unresolved, the presence of a preceding influenza and mumps epidemic is consistent with the dual-pathogen hypothesis, suggesting that interactions between infectious agents may have contributed to the emergence of EL in local hotspots.