BackgroundLeptospirosis is a re-emerging zoonotic disease caused by pathogenic strains of bacteria belonging to genus Leptospira whose symptoms can range from mild clinical manifestations to a severe life threatening illness. This disease may be under-recognized in resource poor settings like Nepal where many clinical laboratories lack appropriate equipment, technology and personnel for proper diagnosis.MethodsWe used IgM ELISA to estimate the sero-prevalence of leptospirosis in a group of febrile patients in a western region of Nepal. We also tested for possible co-infection with two other common febrile diseases endemic to Nepal including dengue and typhoid fever.ResultsAmong samples from 144 febrile patients, 30 (21%) were positive for leptospiral IgM. In univariate analysis, leptospirosis was significantly associated with being of working age (p = 0.019), farming (p = 0.045) and water and animal contact (p = 0.0001). Widal and dengue serological study showed that the majority of leptospirosis infections did not have an alternative diagnosis.ConclusionAs indicated by the study, regular surveillance of animal reservoirs in collaboration with veterinary department and inclusion of leptospirosis as a differential diagnosis of febrile illness is thus recommended based on the current findings.