The largest bivalve in the Mediterranean Sea, the fan mussel Pinna nobilis, is at risk of extinction due to mass mortality events (MMEs) caused by the spread of pathogens, Haplosporidium pinnae in particularly. In spite of being a protected area, Lake Faro (northeast Sicily, Italy) suffers from high anthropogenic pressures that affect the P. nobilis population that inhabits the lake and the two canals that connect it to the sea. In the present study, the population’s long-term changes have been monitored in three distinct periods: before the MME (2010), at the beginning of the epidemic spread along the Italian coasts (2018), and after the MME (2020). The survey, carried out by visual census, showed that, relative to 2010, the population of P. nobilis halved in 2018 and disappeared from the canals in 2020; while in the lake, living specimens were only 27.69 % of the total at this time, without recruits. The disappearance of P. nobilis, allowed rapid colonization by the congeneric Pinna rudis and the invasive oyster Pinctada imbricata radiata, which had never been recorded in the Lake Faro system before 2020.En prens