Oligonol is a low-molecular-weight form of polyphenol and has antioxidant and anti-inflammatory activity, making it a potential promoter of immunity. This study investigates the effects of oligonol supplementation on leukocyte and immune cell counts after heat loading in 19 healthy male volunteers. The participants took a daily dose of 200 mg oligonol or a placebo for 1 week. After a 2-week washout period, the subjects were switched to the other study arm. After each supplement, half-body immersion into hot water was made, and blood was collected. Then, complete and differential blood counts were performed. Flow cytometry was used to enumerate and phenotype lymphocyte subsets. Serum concentrations of interleukin (IL)-1β and IL-6 in blood samples were analyzed. Lymphocyte subpopulation variables included counts of total T cells, B cells, and natural killer (NK) cells. Oligonol intake attenuated elevations in IL-1β (an 11.1-fold change vs.
a 13.9-fold change immediately after heating; a 12.0-fold change vs.
a 12.6-fold change 1h after heating) and IL-6 (an 8.6-fold change vs.
a 9.9-fold change immediately after heating; a 9.1-fold change vs.
a 10.5-fold change 1h after heating) immediately and 1 h after heating in comparison to those in the placebo group. Oligonol supplementation led to significantly higher numbers of leukocytes (a 30.0% change vs.
a 21.5% change immediately after heating; a 13.5% change vs.
a 3.5% change 1h after heating) and lymphocytes (a 47.3% change vs.
a 39.3% change immediately after heating; a 19.08% change vs.
a 2.1% change 1h after heating) relative to those in the placebo group. Oligonol intake led to larger increases in T cells, B cells, and NK cells at rest (p
< 0.05, p
< 0.05, and p
< 0.001, respectively) and immediately after heating (p
< 0.001) in comparison to those in the placebo group. In addition, levels of T cells (p
< 0.001) and B cells (p
< 0.001) were significantly higher 1 h after heating in comparison to those in the placebo group. These results demonstrate that supplementation with oligonol for 1 week may enhance the immune function under heat and suggest a potential useful adjunct to chemotherapy in malignant diseases.