Bonamiosis due to the parasite Bonamia ostreae has been associated with massive mortality in flat oyster stocks in Europe. Control of the disease currently relies on disease management practices and transfer restriction. Previously, massal selections based on survival to challenge to infection with B. ostreae have been applied to produce flat oyster families with resistant progeny. In an attempt to understand the molecular mechanisms involved in disease resistance, differentially expressed sequence tags between resistant and wild Ostrea edulis haemocytes, both infected with the parasite, were identified using suppression subtractive hybridisation. Expression of seven ESTs has been studied using quantitative reverse-transcriptase PCR. The base-line expression of an extracellular superoxide dismutase, inhibitor of apoptosis (OeIAP), Fas ligand (OeFas-ligand) and Cathepsin B was significantly increased, whilst cyclophilin B appeared significantly decreased in resistant oysters. Considering their great interest for further studies, the open reading frames of the OeFas-ligand and OeIAP were completely sequenced. Highlights ► Bonamia ostreae is an intra-haemocytes parasite. ► Flat oyster Ostrea edulis, is the natural host of B. ostreae. ► In this study we have studied genes expressed in response to the parasite. ► Extracellular superoxide dismutase (OeEcSOD) is up regulated in resistant haemocyte. ► Genes involved in apoptosis is up regulated in resistant haemocytes from flat oyster.