A total of 440 Cobb 500 male broiler chicks were used in a 21-day experiment to study how a multi-enzyme influence growth performance, nutrient utilization and short-chain fatty acid (SCFA) profile. Birds were allocated to 8 treatments in a randomized complete block design. Each treatment had 11 replicates with 5 birds per replicate cage. The 8 treatments were based on 4 corn-soybean meal basal diets with different levels of protein and fiber, namely: LFHP (low fiber and high protein), LFLP (low fiber and low protein), HFHP (high fiber and high protein), and HFLP (high fiber and low protein). Each of the basal diets were supplemented with or without multi-enzyme (xylanase and protease). Birds and feed were weighed on days 0 and 21. Excreta, jejunal and ileal digesta, and caeca contents were collected from 6 randomly selected replicates per treatment at the end of the experiment. Weight gain, feed intake and gain: feed were greater (P < 0.05) in birds receiving high protein (HP) diets but enzyme supplementation had no effect. The multi-enzyme increased (P < 0.01) AME and crude protein and DM retention. Birds receiving the HP diets had greater (P < 0.05) AME levels and DM retention. Broilers fed higher fiber had lower (P < 0.01) DM retention and AME. There was significant (P < 0.01) fiber × protein interaction on nutrient utilization; DM retention, N digestibility, and AME were greater in LFHP; however, the reverse was observed for HFHP diets. In addition, there was significant (P < 0.05) protein × enzyme interaction for DM retention and N digestibility. The improvements in N digestibility and DM retention due to enzyme addition was lower in HP diets. Caeca acetate content was lower (P < 0.05) in enzyme-supplemented diets. Weight gain, GF and FBW were significantly positively correlated with acetate. In addition, the CP retention was positively correlated with propionate and valerate whereas AME was negatively correlated with acetate but positively correlated with propionate, isobutyrate and valerate.