The aim of this study was to investigate the effects of different levels of Origanum onites L. essential oil as feed additives on the growth performance, antioxidant activity and disease resistance of rainbow trout. Fish (26.05 +/- 0.15 g) were fed the experimental diets supplemented with four different concentrations (0.125, 1.5, 2.5 and 3.0 mL kg(-1)) of O. onites essential oil for 90 days. Fish fed diets containing essential oil of O. onites had significantly higher final weight than the control group. Feed conversion ratio in fish fed diets containing 1.5 and 3.0 mL kg(-1) essential oil of O. onites was improved than other treatments (P < 0.05). The lowest feed conversion efficiency ratio was recorded in the 0.125 mL kg(-1) group of O. onites. Antioxidant status of fish was assayed for levels of plasma superoxide dismutase (SOD) and plasma catalase (CAT) activity. Lysozyme activity in plasma was significantly higher in fish fed diet containing 3.0 mL kg(-1) essential oil of O. onites (P < 0.05). After 8 weeks of feeding, fish were challenged with Lactococcus garvieae and cumulative mortality was recorded over 15 days. Dietary administration of 0.125, 1.5 and 2.5 mL kg(-1) O. onites significantly reduced fish mortality (P < 0.05). The 3.0 mL kg(-1) diet showed no mortality after challenged with L. garvieae. These results suggested that the essential oil of O. onites could be applied as growth promoter and also improved disease resistance when added to rainbow trout feed.