The present study was conducted to evaluate the effect of various dietary levels of high protein distiller's dried grains (HPDDG) supplemented with enzyme phytase on growth performance, feed utilization and haematological indices of European sea bass Dicentrarchus labrax fingerlings. A total of 150 D. labrax fingerlings with an average body weight of 7.5 ± 0.5g were divided in the five experimental treatments (in triplicates each). The experiment was conducted for 56 days. Fish were fed to apparent the satiation six days a week. Five isonitrogenous 45% CP experimental diets were formulated. The control (C) diet had no high protein distiller's dried grains (HPDDG) and phytase enzyme added. Diet 2 (C+) was formulated as control diet and supplemented with phytase at a level of 0.5 g/kg. Diets 3-5 each contained HPDDG at levels of 20, 30, and 40 %, respectively with soybean meal and supplemented each with phytase at a level of 0.5 g/kg. Over the 56 days feeding period, all fish fed HPDDG-supplemented with phytase diets resulted in higher growth than the control diet, suggesting that the using of HPDDG-supplemented with phytase enhanced the growth performance of sea bass fingerlings. The same trend was recorded for the best FCR and PER. The hematology and serum biochemistry (hemoglobin (Hb), red blood cells (RBCs) count, white blood cells (WBCs) and hematocrit (Hct %) and immune parameters (total protein, albumin, globulin, cholestorl, lysozyme activity and total antioxidant capacity) of D. labrax fingerlings significantly (P ≥ 0.05) increased with increasing dietary HPDDG with phytase. Result indicates that HPDDG with phytase is a good alternative protein source for compromising growth performance and physiological parameters of European sea bass, Dicentrarchus labrax Fingerlings