This updated scientific opinion on oyster mortality addresses 1) the role of ostreid herpesvirus (OsHV-1) in mortality, 2) evidence for a role of Vibrio aestuarianus in mortality, 3) effectiveness of water treatment in inactivating OsHV-1 and V. aestuarianus and 4) feasibility, availability and effectiveness of the disease prevention and control measures. A new pattern of mass mortality of Pacific oysters (C. gigas) was observed in France and other European countries from 2008 onwards. Similar outbreaks were reported in 2010-11 from Australia and New Zealand. Studies performed since 2010 has provided strong evidence that OsHV-1 μVar is causally linked to increased oyster spat mortality at sea water temperatures above 16 °C. V. aestuarianus subsp. francensis was detected in France in 2001 in moribund oysters; since then this bacterium has been regularly detected during oyster mortality events. Owing to a lack of information, the causal relationship between V. aestuarianus and oyster mortality has not been established. Discharge of untreated seawater from depuration plants remains a potential mode of transmission of diseases affecting bivalves and other marine life. Effective disinfection of seawater effluent from depuration and holding facilities will minimize the risk of transmission of infectious agents. Unrestricted movement of oysters is associated with a high risk of spread of OsHV-1. Wild populations of C. gigas also contribute to spread of OsHV-1. Only a few areas in Europe continue to remain free from OsHV-1. Once infected, an area is not likely to regain freedom from OsHV-1 if a wild population of C. gigas is present. Almost all OsHV-1 strains isolated after 2008 conform to the definition of microvariants. Therefore, it appears unnecessary to maintain a separate definition of microvariants for disease control purposes. The criteria in Directive 2006/88/EC for listing of non-exotic diseases are currently not fulfilled for mortality caused by OsHV-1 microvariants.