We investigated the changes in percentages of leukocyte subpopulations, natural killer (NK) cells, CD69-expressing lymphocytes, and psychological aspects in 10 subjects who participated in a 10-day confinement study. Suppression of lymphocyte proliferative reaction and changes in leukocyte distribution are known to occur in space. These responses are similar to those induced by psychological stress. Ground-based confinement studies are suitable for validating the effects of stress arising only due to confinement. Two groups consisting of 5 male subjects (ages 20 -27, mean 22.8), each participated in a 10-day confinement study. Blood samples were taken once before, 3 times during, and once after the confinement and activated with an anti-CD2 agonistic antibody cocktail. The percentage of leukocyte subpopulations, NK (CD45+CD56+) cells, and activated lymphocytes (CD45+CD69+) were measured by flow cytometric assay. The face scale test was used to measure psychological aspects. The percentage of CD69-positive lymphocytes decreased during the period of confinement. This was mostly caused by changes in the ratio between NK and non-NK lymphocytes. The face scale showed that the subjects' mood improved toward the post-confinement period. Consistent with the face scale, the percentages of innate immune cells, such as NK cells and granulocytes, increased during the post-confinement period. We concluded that the changes in the distribution of immune cells caused by stress plays an important role in suppression of proliferative reactivity. The observed physiological reactions were specific to the confined environment and the stress caused by confinement plays a role in the immune changes observed in space.