<p>This study investigated the influence of meat and bone meal (<b>MBM</b>), phytase, and antibiotics (<b>AB</b>) on the performance, intestinal pH, ileal digestibility, cecal microbiota, and tibial mineralization in Ross 308 broilers challenged with necrotic enteritis (<b>NE</b>). A total of 672-day-old male Ross 308 chicks were allocated to 8 treatments with 6 replicate pens, with 14 birds each. The study employed a 2 × 2 × 2 factorial arrangement of treatments: MBM (no or yes), AB (no or yes, zinc bacitracin + salinomycin), and phytase level (500 or 1,500 FTU/kg; both using 500 matrix recommendations). Diets were based on wheat-soybean meal-canola meal. All birds were challenged with <i>Eimeria</i> spp on day 9 and <i>Clostridium perfringens</i> (<i>C. perfringens</i>) strain EHE-NE18 on day 14 and day 15. On day 21 (postchallenge), birds fed MBM had reduced weight gain (WG; <i>P</i> < 0.05) relative to without MBM. A 2-way phytase × AB interaction for WG on day 14 (<i>P</i> < 0.001) and day 21 (<i>P</i> < 0.001) and feed conversion ratio on day 21 (<i>P</i> < 0.001) and day 42 (<i>P</i> < 0.01) indicated positive effects of high phytase on bird performance in the presence of AB. On day 42, a 3-way MBM × phytase × AB interaction (<i>P</i> < 0.01) was observed for WG, showing high phytase increased WG with AB, relative to the birds without AB in the presence of MBM. A 2-way MBM × phytase interaction (<i>P</i> < 0.01) was observed for apparent ileal digestibility of Ca and P on day 16, whereby there was a notable reduction in Ca and P digestibility in birds fed MBM-free diets and a low phytase level, but with the high phytase level, Ca and P digestibility was not influenced by MBM. In conclusion, in NE challenged birds, high phytase has a beneficial effect on leg health and mineral utilization to the extent that it can replace MBM and has beneficial effects on bird performance in the presence of AB.</p>