The Seine estuary, one of the largest estuaries of the European northwest continental shelf, is subjected to numerous anthropogenic influences. Here we present an assessment of the microbial faecal contamination of the estuary water. The most vulnerable areas were defined on the basis of the fluxes of indicator organisms and the occurrence of Salmonella and Cryptosporidium sp. and Giardia sp. (oo)cysts. The microbial quality of the water changes from upstream to downstream: in the upstream area, contamination by faecal-indicator bacteria and Salmonella occurs during periods of high flow; in the urbanized area, mid-way between the uppermost areas of the estuary and its mouth, discharge from a wastewater treatment plant and a tributary degrade water quality; at the estuary mouth, the accumulation of microorganisms attached to particles in the maximum turbidity zone, particularly Clostridium perfringens spores and oocysts of Cryptosporidium, is accompanied by inputs of ThC and Escherichia coli from tributaries. In some areas, significant strong relations are observed between Salmonella, (oo)cysts of protozoan, and levels of faecal indicators.