Direct-fed microbials (DFM) are used to improve livestock health and performance. The effects of 2 DFM products, a blend of 3 Bacillus strains (DFMB) and a Propionibacterium spp. (DFMP), on broiler performance, nutrient utilization, and immune responses were investigated. Day-old (n = 120) male broilers were divided into 24 groups of 5 birds and fed 3 wheat-based diets in mash form (8 groups per diet) from d 1 to 22. The control diet was fed without or with 7.5 × 104 cfu/g of either DFMB or DFMP. From d 19 to 21 fecal samples were collected for determination of total tract apparent retention (TTAR) of nutrients and AMEn. On d 21, feed intake and BW were determined. On d 22, 5 birds per treatment were killed by cervical dislocation to collect jejunal and ileal contents for determination of digesta viscosity and apparent ileal digestibility (AID) of nutrients, respectively, and ileum, cecal tonsil, and spleen tissues for Toll-like receptors (TLR) and cytokine expressions. Compared with the control, DFM did not affect BW gain and feed intake but DFMP reduced G:F (P < 0.01). Compared with the control (2,875 kcal/kg), birds fed on DFMB and DFMP had higher AMEn (2,979 and 2,916 kcal/kg, respectively; P < 0.05), whereas both DFM reduced the AID of DM (P < 0.001) and CP (P < 0.01). Furthermore, DFMP reduced TTAR of NDF (29.0 vs. 18.4%; P < 0.001), whereas both DFM increased TTAR of DM and fat (P < 0.001). Supplementing DFMP downregulated ileal expression of TLR-2b, IL-2, IL-4, IL-6, IL-10, and IL-13, whereas DFMB downregulated TLR-2b, IL-2, IL-4, and IL-6 in all 3 tissues, IL-10 in the spleen, and upregulated IL-13 in the spleen. In conclusion, the DFM did not improve performance but increased the AMEn of diet by possibly increasing DM and fat retention. Overall, both DFM showed an antiinflammatory effect in the ileum, but DFMB had more effects on local and systemic immunity than DFMP. © 2014 Poultry Science Association Inc.