Experiments were conducted to investigate the effects of farming sites, seeding date, age of oysters, ploidy level and rearing structures on mortality, pathogens and energetic reserves of oysters Crassostrea gigas. Mortality of oysters coincided with infections involving, primarily, the ostreid herpesvirus OsHV-1 and, secondarily, bacteria of the group Vibrio splendidus, when seawater temperature was between 17 and 24°C. Mortality started in early May and lasted until late September, with an interruption in July and August when seawater temperatures rose above 24°C. Mortality varied with farming site: oysters maintained in the open Mediterranean Sea showed no mortality and OsHV-1 was occasionally detected at a low level only, while oysters maintained in the farming area of the Thau lagoon exhibited mass mortality events concomitantly with outbreaks of OsHV-1. Mortality of oysters maintained in the Thau lagoon but outside the oyster farming area was sporadic and coincided with currents coming from the farming area where mortality was occurring. Mortality of oysters also varied with farming practices. Naïve oysters remained susceptible to pathogen-related mortality pressure during their first 2 yr, whereas oysters that had survived a mass mortality event in the past appeared resistant. Mortalities of diploid (2n) and triploid (3n) oysters were similar during spring but mortalities of 2n oysters were double those of 3n oysters during summer and autumn. Finally, oysters grown in Australian baskets suffered 80% mortality compared with only 30% among oysters cemented onto ropes. The effects of farming practices on mortality are discussed in relation to pathogens and energetic reserves of oysters.