Leptospirosis is a zoonotic disease that can be transmitted by contact with the urine of infected mammals. Rodents play a mayor role in the transmission of leptospires to humans. The province of Santa Fe reports the greatest number of cases in Argentina. Yet, in this region, there are still knowledge gaps regarding the diversity of rodent species that may be hosts of pathogenic leptospires. The aims of this study were to evaluate the presence of leptospiral antibodies in rodents from three riverside communities of Santa Fe, and to identify factors associated with leptospiral infection.