A 21-d experiment was conducted to study the effect of xylanase, protease, and xylo-oligosaccharides on growth performance, nutrient utilization, gene expression of nutrient transporters, cecal short-chain fatty acids (SCFA), and cecal microbiota profile of broilers challenged with mixed Eimeria spp. The study utilized 392 zero-d-old male broiler chicks allocated to 8 treatments in a 4 × 2 factorial arrangement, as follows: corn-soybean meal diet with no enzyme (Con); Con plus xylanase alone (XYL); Con plus xylanase combined with protease (XYL + PRO); or Con plus xylo-oligosaccharides (XOS); with or without Eimeria challenge. Diets were based on a high-fiber (100g/kg soluble fibers and 14g/kg insoluble fibers) basal diet. At d 15, birds in challenged treatment were gavaged with a solution containing Eimeria maxima, Eimeria acervulina, and Eimeria tenella oocysts. At d 21, birds were sampled. Eimeria depressed (P < 0.01) growth performance and nutrient utilization, whereas supplementation had no effect. There were significant Eimeria × supplementation interactions for the sugar transporters GLUT5 (P = 0.02), SGLT1 (P = 0.01), SGLT4 (P < 0.01), and peptide transporter PepT1 (P < 0.01) in jejunal mucosa. Eimeria challenge increased the expression of GM-CSF2 (P < 0.01) and IL-17 (P = 0.04) but decreased (P = 0.03) IL-1β expression in the cecal tonsil. Eimeria × supplementation interactions for cecal acetate, butyrate, and total SCFA showed that concentrations increased or tended to be greater in the supplemented treatments, but only in non-challenged birds. Birds challenged with Eimeria spp. had higher concentrations of isobutyrate (P < 0.01), isovalerate (P < 0.01), and valerate (P = 0.02) in cecal content. Eimeria challenge significantly (P < 0.01) decreased the microbial richness and diversity, and increased (P < 0.01) the proportion of Anaerostipes butyraticus, Bifidobacterium pseudolongum, and Lactobacillus pontis. In conclusion, Eimeria infection depressed growth performance, nutrient utilization with regulating nutrient transporters. Furthermore, Eimeria challenge shifted the microbial profile and reduced microbial richness and diversity. On the other hand, enzyme supplementation showed limited benefits, which included increased concentrations of SCFA.