Mediterranean mussel (Mytilus galloprovincialis) is a species of bivalve mollusk that has a high capacity in filtering the water nearby and concentrate the virus and bacteria present in it. This can constitute a microbiological risk when they are consumed afterwards. Thus, depending on water pollution, mussels suffer a depuration process, usually controlled using Escherichia coli as indicator. The aim of this study was to determine the microbiological quality of mussels from various sources after purifying, and to consider the utility of the use of Clostridium perfringens as quality indicator. For this, microbiological analysis were performed in fifteen lots of mussel samples obtained from Spain and Italy. Aerobic mesophilic microorganisms, Enterobacteriaceae, E. coli, Vibrio spp., Listeria monocytogenes, Cl. perfringens, and the presence Salmonella spp. were measured. The results showed the presence of Salmonella spp. in four batches of mussels from various locations and Cl. perfringrens in thirteen of them. All samples were within the legal limits for E. coli. In conclusion, the results propose that the use of E. coli as an indicator microorganism for the mussels' depuration process is not sufficient to assure the microbiological quality of the product. Thus, it would be appropriate to include of Cl. perfringens, as an additional indicator, in the control carried out during and after the refinement is done. Finally, the results emphasized the necessity to properly cook this food product prior to consumption, as it allows the destruction of any microorganisms present.