Mussels are a group of sessile and filter-feeding invertebrates, and are key structural elements of many marine and freshwater ecosystems. The mussel haemolymph is the first defense line to pathogen infection and inflammation with an innate immune response. Despite the importance of this body fluid in determining the physiological condition of the animal, little is known about the molecular mechanisms underlying the cellular and humoral responses. Proteomic characterization of this body fluid has been hampered by the scarce Mytilus sp genomic data available. To systematic characterize the marine mussel Mytilus edulis hemolymph proteome, we have applied a mass spectrometry (nanoLC-MS/MS) strategy integrating genomics and transcriptomics data for proteins identification. After sample analysis and first identification based on MS/MS data comparison, proteins with unknown functions were annotated with blast using public database (nrNCBI) information. Overall 654 haemolymph proteins were identified with high confidence. The gene ontology analysis revealed that the majority of haemolymph proteins participate in primary cellular metabolic processes: energy production and metabolism of biomolecules. Nevertheless it also revealed a protein complement whose functions could be related to oxidative stress defense, xenobiotic detoxification, drug metabolism and immune response.