This study evaluated the effect of yeast-derived products on growth performance, serum antibody levels, and mRNA gene expression of pattern-recognition receptors, and cytokines in broiler chickens. Two hundred and sixteen one-day-old male broiler chickens (Ross-308) were randomly assigned to six dietary treatments with six replicates (cage) of 6 birds per cage. Dietary treatments consisted of a Control diet without antibiotics (C), and diets containing 11 mg/kg of “virginiamycin”, 0.25% of yeast cell wall (YCW), 0.2% of a commercial product “Maxi-Gen Plus” containing processed yeast and nucleotides, 0.05% of nucleotides, or a diet containing 8% of distiller's dried grains with solubles (DDGS). On d 21 post-hatch blood samples were collected from 6 birds per treatment and serum sample were analyzed for antibody levels. After blood sampling, birds were injected intraperitoneally with 3 mg/kg of BW of lipopolysaccharide (LPS). The unchallenged group was fed the Control diet and injected with saline solution. Spleen samples were collected to measure the gene expression of toll-like receptors (TLR)2b, TLR4, and TLR21, macrophage mannose receptor (MMR), and cytokines including interleukin (IL)-12, IL-10, IL-4, IL-6, IL-18, and interferon (IFN)-γ. No significant difference in body weight gain, feed intake, and FCR were observed among treatments. Regarding humoral immunity, the diet supplemented with YCW increased serum immunoglobulin (Ig)A level compared with the antibiotic group; however, serum concentrations of IgG and IgM were not affected by dietary treatments. Relative gene expression of TLR2 and TLR4 was not affected by dietary treatments, whereas the expression of TLR21 and MRR was upregulated in diets containing YCW and DDGS. The diet supplemented with YCW increased the expression of all cytokines, and expression of IFN-γ was upregulated in the DDGS group. However, no significant difference was observed for cytokine gene expression in the antibiotic and nucleotide diets. In conclusion, supplementation of diet with YCW stimulated the systemic innate immune responses of broiler chickens following challenge with LPS.