The objective of this study was to evaluate the effects of cottonseed meal (CSM) treated with sodium bentonite (SB) on certain blood components and immune response of laying hens. A 3 × 3 factorial arrangement with 3 levels of SB (0, 10, and 20 g/kg of diet) and 3 levels of CSM (0, 100 and 200 g/kg of diet) were used within 9 dietary treatments of 4 replicates each. Nine mash diets were fed to 288 commercial Hy-Line W-36 hens from 51-63 weeks of age. Blood samples were collected at the end of trial to evaluate the blood constituents. The SB, CSM, or their interaction (SB×CSM) did not have any adverse effect on blood cells and activity of serum enzymes. Sheep red blood cells (SRBC) were used as antigen to quantify the antibody response. Two birds per replicate were injected with SRBC at 60 week of age. After 7 and 14 d of SRBC inoculation, blood samples were obtained from the brachial vein of each hen, and total anti-SRBC, IgG and IgM titers were determined. A significant difference of SB, CSM or their interaction was not observed for total antibody response against SRBC inoculation; however, IgG was significantly increased with 20% CSM at 7 d (7.62 vs. 8.45) and with 2% SB at 14 d (2.79 vs. 3.66) after injection of SRBC. The interaction of SB and CSM for IgG was significantly different among dietary treatments and diet with 2% SB and 20% CSM had the highest titer (5 vs. 2.5) at 14 d after injection of SRBC. In conclusion, SB, CSM or their interactions did not affect blood constituents but significantly changed immune response of the birds. Manuscript profile