Background: The pollution of water bodies is a serious concern in most rural areas in low- and middle-income countries due to anthropogenic activities which pose the greatest risk of human hepatitis viruses to public health. The aim of the study was to determine the probability of hepatitis A virus (HAV) infection associated with human consumption of water from River Owena, Nigeria. Methods: Water samples were collected from points with intense anthropogenic activities during dry and wet periods. Loads of enteric bacteria and HAV were determined using culture-based method and molecular technique. Risks of HAV infection was estimated using dose-response model, and probabilities of clinical illness and mortality were also determined. Results: Results revealed that the levels E. coli and faecal coliforms were greater during the wet period than the dry period (p< 0.05). Concentration of HAV was greater during the dry period than the wet period (p< 0.05). Risks of HAV infection were higher during the dry period than the wet period, and were all above the US EPA acceptable risk limit. Risk of clinical illness and mortality due to HAV were higher during the dry period than the wet period. Conclusions: Ingestion of water from the river may result into liver inflammation, morbidity or death. Development of active water management plans to reduce pollutant fluxes and address contamination threats must be established.