Background It is well known that dehydration can impair bodily functions. To evaluate the impact of hydration status under ambient environmental temperature on the immune system, 25 male collegiate wrestlers were recruited to undergo an experimental dehydration program.Methods Thirteen subjects had controlled diets with individual energy requirements to prevent body mass loss and restricted water intake to cause 4.52% dehydration; they formed the dehydrated group (DE). These subjects developed a urine specific gravity of about 1.030 in 84 hours. Twelve other subjects had no water restriction and maintained their total body weight comprised the euhydrated group (EU). Peripheral blood monocytes (PBMNC) were isolated after dehydration to perform immune response testing by being incubated with a polysaccharide fraction from fu-ling, Poria cocos (polysaccharide fraction from Poria cocos, PCPS, 1-30 μg/L), to prepare a conditioned medium termed conditioned medium of PBMNC stimulated by PCPS (PCPS-MNC-CM). More PCPS (25 μg/L) was needed in the DE group to prepare the PCPS-MNC-CM, which was assayed with a growth inhibitory curve for treated U973 cells.Results The treated U937 cells, incubated together with PCPS-MNC-CM from the DE group, exhibited a much lower nitroblue tetrazolium (NBT) positive value of (63.7±4.7)%. The concentration of interferon-gamma (IFN-Y), interleukin (IL)-1β and tumor necrosis factor (TNF)-α in PCPS-MNC-CM from subjects after dehydration was much lower than in the CM from the EU group.Conclusion The immune response to PCPS in the DE group was lower than in normally hydrated subjects.