Significant mortality of trestle-cultured Crassostrea gigas during the summer months is a widespread and complex phenomenon. Hatchery-produced C. gigas seeds were trestle-cultured at Bannow Bay and Dungarvan Harbour in Ireland and the Menai Strait and Inland Sea in Wales in 2003 and 2004. Environmental parameters of temperature, chlorophyll a, coloured dissolved organic matter (cDOM), inorganic nutrients (phosphate, nitrate, nitrite), ammonium, silicate and dissolved organic nitrogen were measured fortnightly during the summer. Mortalities were monitored regularly and samples of blood were taken for investigation of some immune parameters (haemocytes ml− 1 and percentage granulocytes). In 2003, mass mortality event (> 20%) of oysters occurred at two sites in Ireland. Field measurements indicated that high temperature and high nutrients in combination may have contributed to that mortality event. Laboratory experiments demonstrated that oysters were immuno-compromised at a temperature of 21 °C compared with 12 °C exhibiting reduced numbers of haemocytes ml− 1 and decreased phagocytosis activity in blood. Experimental addition of inorganic nutrients at field-measured concentrations (15 µM phosphate, 278 µM nitrate, 5.14 µM nitrite) caused significant oyster mortality at a temperature of 21 °C but not at 12 °C. Results demonstrate that causes of C. gigas mortality are multifactorial and water quality and increased temperatures may contribute to the complex causes of significant mortalities.