We previously reported that a low-protein soybean meal, LPSBM vs. high-protein SBM (HPSBM), produced greater body weight in the starter phase of broiler chickens and marginally higher body weight on d42 in cocci-challenged broilers. This study investigates possible mechanisms accounting for the differences in performance we reported. A 42-day floor pen trial with 10 treatments and 6 replicates/treatment with 15 birds/replicate was used to study the objective. Treatments were arranged in a 5 × 2 factorial with factors as diets (5 diets) and cocci (challenge; CH vs. no challenge; NCH). Diets were: 1. LPSBM, 43% CP; LPSBM was prepared by mixing soy hull (SH) with HPSBM, 48% CP; 2. corn-HPSBM diet; 3. corn-LPSBM + xylanase, 4. HPSBM+ 5% wheat bran (WB) and 5. HPSBM+ xylo-oligosaccharides. All the diets were isonitrogenous and isocaloric with the same level of digestible AA. Birds in CH group were challenged with a mixture of Eimeria species on d15, while NCH group received tap water. At day 21, ileal digesta were collected to determine ileal amino acid digestibility (IAD). Jejunum tissue was collected for histology and mRNA expression of nutrient transporters and tight junction genes, and breast tissue for protein synthesis (mTOR, EEF2, 4EBP1) and degradation genes (Myog, MYF5, FBX09). Cocci challenge decreased (P < 0.05) IAD of all the AA. Threonine digestibility was greater (P < 0.05) for LPSBM and LPSBM+ xylanase than for other diets. The villi were shorter, and crypts were deeper (P < 0.05) in the CH group. Cocci challenge increased P < 0.05) claudin and GLUT1 mRNA expression but decreased (P < 0.05) expression of Bo+AT. There was higher mTOR and MYF5 (P < 0.01) expression in CH. There was significant diet × cocci for expression of EEF2, 4EBP1, Myog, and FBXO9 (P < 0.05). There was a decrease in mRNA of EEF2, 4EBP1, and FBXO9 in NCH group. However, in the CH group, LPSBM + xylanase tended to decrease the mRNA expression of the genes.