This study was carried out to study the effect of enzymes mixture and phytase supplementation in sorghum-soybean meal diets on some physiological responses of broiler chicks. One hundred ninety-two, unsexed, day old Hubbard broiler chicks were randomly distributed into six groups with four replicates each with eight chicks. Three diets from each of the starter and grower based on sorghum- soybean meal were formulated to have either recommended, medium or low levels of both crude protein and metabolizable energy. The first starter and grower diets were served as control dietary treatment (D1). The second (D2) and third (D3) starter and grower diets were formulated to have gradually decreased levels of both crude protein by 2% and 4% and metabolizable energy 300 and 600 kcal/kg for diet D2 and D3, respectively. Starter and grower diets were supplemented with or without enzymes. The data reviled that, values of serum glucose, total protein and it's fractions (albumin and globulin), total lipids, calcium and phosphorus(mg/dl) were increased (p<0.05) with enzymes supplementation. However, liver enzymes (ALT and AST) and thyroid hormones (T3 and T4) of broiler chicks were not significantly affected by cocktail enzymes supplementation. While, the activity of ALT was decreased (p<0.05) with decreasing CP% and ME level by 2% and 300 kcal/kg, respectively less than the recommended level, but no further decrease in ALT activity was observed by decreasing CP% and ME energy beyond the previously mentioned level. However, AST activity showed no clear trend in relation to the level of both protein and energy. From the present results, it can be concluded that using mixture and phytase enzymes into sorghum-soybean meal diet could be lead to improvement on some physiological responses of broiler chicks.