Undigested proteins entering the hindgut may favor the proliferation of Clostridium perfringens. Using phytase to eliminate the need for meat and bone meal ( MBM) as a P source may reduce potential infection with C. perfringens. A study was conducted to determine the impact of MBM, phytase, and antibiotics ( AB) on intestinal permeability and morphology, organ weights, and jejunal gene expression in Ross 308 chickens challenged with subclinical necrotic enteritis ( NE). Male Ross 308-day-old chicks (672 each) were randomly allocated to 8 treatments with 6 replicate pens each housing 14 birds. A 2 × 2 × 2 factorial arrangement of treatments was used: MBM (no or yes); AB (no or yes—Zn bacitracin 100 in S and 50 ppm in G/F and salinomycin Na 60 ppm in all phases); phytase (500 or 1,500 FTU/kg, both using 500 FTU matrix values) using wheat-SBM-canola meal diets. Birds were challenged with Eimeria spp on day 9, and C. perfringens strain EHE-NE18 on day 14 and 15. An AB × MBM interaction ( P < 0.05) was detected for relative gizzard weight (with contents) being lower in birds fed MBM and AB compared to those fed MBM and no AB. A MBM × AB interaction ( P > 0.01) was detected for lymphocyte counts being lower with MBM and AB compared to MBM without AB. A phytase × AB interaction ( P < 0.05) was observed for villi length being increased with high phytase and no AB compared to with AB. Inclusion of MBM increased ( P < 0.05) blood FICT-d concentration, whereas AB decreased it ( P < 0.05). Antibiotics increased RBC ( P < 0.05), Hgb ( P < 0.05), and PCV ( P < 0.05) and expression of Ca-binding protein, CALB1 ( P > 0.05). Inclusion of MBM decreased expression of MUC2 ( P < 0.05). Results indicate that dietary MBM has a detrimental effect on gut health of broilers but this may be counteracted using AB.