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The present study was conducted to determine whether the addition of β-mannanase in broiler feed changes hormonal profiles in the blood and broiler performance and nutrient availability. Five hundred and four Cobb male chickens were studied during d 7 to 21. Three corn-soybean meal (SBM) based diets 1) Low SBM (18% SBM); 2) High SBM (31% SBM); and 3) High SBM+GG (31% SBM + Guar Gum (GG) 0.5%) with 3 levels of β-mannanase (0, 200, and 400 ppm) were mixed to produce 9 diets. A factorial design 3 × 3 was performed with JMP pro 13 (SAS, 2017). Analysis of variance and contrast analysis were used to test significance level at P < 0.05. Glucose (190 and 188 mg/dL) was increased with 200 and 400 ppm of β-mannanase, respectively, compared to control (182 mg/dL) in the fasted state (P < 0.037). Glucose was higher in chicks fed with the High SBM and High SBM + GG diets but lower in the fasted re-fed state (P < 0.01). Insulin was higher with 200 and 400 ppm added β-mannanase in the fed state (P < 0.021). Insulin-like growth factor-1 was higher with 400 ppm added to High SBM+GG. β-mannanase improved feed conversion ratio (FCR) 9 points with 400 ppm in High SBM diet (P < 0.01) and 16 and 18 points with 200 and 400 ppm, respectively, added to the High SBM+GG diet (P < 0.01). Viscosity decreased from 19.2 to 7 cps with both enzyme doses in the High SBM + GG diet (P < 0.01). Digestible energy was +152 kcal/kg with 400 ppm β-mannanase in the High SBM diet and +200 kcal/kg with both levels of enzyme in High SBM+GG diet. Digestibility of amino acids was improved from 0.8 to 3.6% with β-mannanase in High SBM+GG diet (P < 0.05). In conclusion, chicks fed with High SBM and High SBM+GG diets with added β-mannanase significantly improved blood glucose and anabolic hormone homeostasis, FCR, digestible energy, and digestible amino acids compared to chicks fed with same diets without β-mannanase.