Ozone is claimed to have beneficial effects. While studies revealed the safe therapeutic use of ozone, there are conflicting results for the link between immune system and ozone encounter. Natural killer (NK) cells are important sentinels of immunity with their cytotoxic activity and immune-regulatory potentials. This study aimed to investigate the effects of direct ozone encountering on human immune system, at cellular level. Survival, proliferative capacity and subset content of peripheral blood mononuclear cells (PBMC) were analysed. PBMC of healthy donors (n=5, mean age: 27±6 years) were exposed to 1, 5, 10 and 50 µg/mL doses of medical ozone, directly injected into culture wells, once, initially. 1 and 5 µg/mL doses didn't show toxic effects while 10 and 50 µg/mL doses were toxic. PBMC were cultured for 5 days following 1 and 5 µg/mL ozone encountering. 1 µg/mL dose increased numbers of CD3-CD16+/56+ NK cells among PBMC. Following stimulation with ozone, no difference was observed in basal and phytohemaglutinin-stimulated proliferative capacity. 1 and 5 µg/mL doses of ozone were found to increase NK cytotoxicity. These data indicates influential effects of transient ozone exposure on NK cells, which in turn may have a role in control of immune responses.