This study investigated the effect of Escherichia coli-derived phytase under the brand name Phyzyme® XP (PHZ) on the efficiency of substituting part of fish meal (FM) with soybean meal (SBM) within six treatments, including control (S0) (basal diet containing FM), S0P (basal diet + 0.02% PHZ), S20 (20% SBM), S20P (20% SBM + 0.02% PHZ), S40 (40% SBM), and S40P (40% SBM + 0.02% PHZ) in juvenile Caspian brown trout (Salmo trutta caspius Kessler, 1877) weighing 148.1 ± 2.98 g for 12 weeks. The S0 and S0P treatments had the best growth performance with a significant difference compared to the S40 and S40P treatments (P < 0.05). Serum glucose level in the S0 treatment showed a significant decrease compared to S40 and S40P treatments (P < 0.05). Decreased cholesterol and increased total immunoglobulin in the serum of S20, S20P, S40, and S40P treatments were significant compared to the S0 (P < 0.05). Serum triglyceride levels increased significantly in the S20, S40, and S40P treatments compared to the S0 (P < 0.05). The decrease in liver activity of superoxide dismutase and glutathione peroxidase and also the significant increase in liver activity of malondialdehyde in the S40 and S40P treatments were significant compared to the S0 (P < 0.05). The apparent digestibility coefficient of dry matter was significantly increased in the S20, S20P, S40, and S40P treatments compared to the S0 and S0P treatments (P < 0.05). The highest body muscle protein was observed in the S0P treatment, which was significant compared to the S40 treatment (P < 0.05). The results showed that the addition of 0.02% PHZ to the diet replaced with 20% and 40% SBM instead of FM seems no any benefit for the fish. It is suggested to study Phyzyme® XP in doses higher than 0.02% to reduce the negative effects of SBM in the diet more clearly.