Since 2008, mass mortalities of 1-yr-old oysters, Crassostrea gigas, associated with ostreid herpes virus OsHV-1 μVar, have occurred along all coasts of France and later in several other countries. The effect of four salinities, namely 10, 15, 25, 35 ppt, were tested on disease transmission and related mortalities in acclimated and non-acclimated oysters. Four-month-old naïve oysters were infected with water coming from tanks where field-infected animals were maintained. The results showed that the odds of mortality were much lower at 10 ppt than that observed in other salinities for acclimated oysters. However for non-acclimated animals, odds of mortality at 10 ppt were much higher than that observed at other salinities, likely reflecting the effects of stressful environmental condition combined with infection. Levels of OsHV-1 DNA were lower in oysters maintained at 10 ppt compared to that of animals held at 15-35 ppt. Therefore, it seems that low salinity could protect acclimated oysters from mortalities, as previously reported for the oyster Crassostrea virginica and its parasites. It was also observed that oysters acclimated at 10-15 ppt were smaller than those held at 25-35 ppt. The combined effects of salinity and infection on oyster physiology are now being investigated.