Pesticide usage in Delta del Ebro (NE Spain) during the rice growing season has been associated with oyster episodes of mortality that occur early in summer. However, there are no studies that have directly evaluated pesticide levels and effects in oysters (Crassotrea gigas) cultured in Ebro's Bays. In this study pesticide levels in water, metal body burdens and up to 12 different biochemical markers were monitored in gills and digestive glands of oysters transplanted from May to June in 2008 and 2009. Biochemical responses evidenced clear differences in oysters from 2008 and 2009. Oysters transplanted in 2009 showed their antioxidant defenses unaffected fromMay to June and consequently increased levels of tissue damagemeasured as lipid peroxidation and DNA strand breaks and ofmortality rates. Conversely oysters transplanted in 2008 increase their antioxidant defenses from May to June, had low levels of lipid peroxidation and DNA damage and lowmortality rates. Some pesticides in water such as bentazone and propanil together with high temperatures and salinity levels were related with tissue damage in oyster transplanted in 2008 but the observed large differences between years indicate that abiotic factors alone could not explain the high mortalities observed in 2009. An analysis of recent reported studies pointed out in the direction that in addition to abiotic factors the use of oysters sensitive to diseases may explain the observed responses