Aims The Thau lagoon shellfish are regularly impacted by microbial pollution of faecal origin, which cause European health standards to be exceeded and closure of the shellfish harvest. The aims of this study were to investigate the impact of weather and hydrological conditions on Escherichia coli (E. coli) accumulation factor (AF) between water and oysters and to evaluate the relevance of the use of this ratio for the purpose of sanitary risk assessment. Methods and results Water and oysters (Crassostrea gigas) were sampled simultaneously in situ during 18 months in periods of dry weather and after rainfall events. Shellfish sanitary thresholds were exceeded in both periods. The E. coli AFs measured after rainfall (median = 6) were lower than in dry weather (median = 32), suggesting different shellfish faecal contaminations were operating in this system process. Conclusion The AFs we measured appeared to be relevant markers for generating sanitary risk assessments for Thau lagoon shellfish. Significance and impact of the study The results of the study address the need to assess the relationship between water quality measures and shellfish flesh quality. This study will contribute to the elaboration of a management tool to guide local authorities in prioritizing the sources of pollution and in optimizing public investment in the watershed.