Extreme climatic events (ECE) are beginning to be perceived as potential causes of health disturbances. The assessment of the impacts of certain ECE to human health has become essential to health managers and caregivers. The objective of this study was to identify the association between rates of hospitalization for Leptospirosis and the occurrence of extreme hydrological events in the state Santa Catarina (Brazil) between the years 2005 and 2014. The association between Leptospirosis hospitalizations and the occurrence of floods, flash floods, and flooding events was measured through Spearman’s bivariate correlation coefficient. Flash floods corresponded to 92.6% of the total hydrological events. Coastal regions presented higher admission rates than inland. The Leptospirosis presented a seasonal pattern, with a peak in the summer months. Positive and significant correlations for monthly and annual analyzes were identified for some of the analyzed macro-regions, with higher values of correlation in the coastal region. The current results suggest the influence of the occurrence of extreme hydro-meteorological events on the variability of the hospitalization rate by Leptospirosis in the state of Santa Catarina, with significant differences found for the coastal and inland regions.