In 2014, a high and unusual mass mortality of mussels occurred in several important production areas along the French coasts of the Atlantic and English Channel. In the first quarter of 2016, mass mortalities hit farms on the west coast of the country once again. These heterogeneous mortality events elicited a multi-parametric study conducted during the 2017 mussel season in three sites in northern Brittany (Brest, Lannion and St. Brieuc). The objective was to assess the health status of these mussels, follow mortality and attempt to identify potential causes of the abnormal high mortality of farmed mussels in northern Brittany. Brest was the most affected site with 70% cumulative mortality, then Lannion with 40% and finally St. Brieuc with a normal value of 15%. We highlighted a temporal ‘mortality window’ that opened throughout the spring season, and concerned the sites affected by mortality of harmful parasites (including pathogenic bacteria), neoplasia, metal contamination, and tissue alterations. Likely, the combination of all these factors leads to a weakening of mussels that can cause death.