To investigate the relationship between natural killer(NK) cells and traumatic brain injury(TBI), we tracked an established phenotype of circulating NK cells at several time points in patients with different grades of TBI. In serial peripheral blood samples, NK cells were prospectively measured by flow cytometry of CD3-CD56+ lymphocytes. Compared to healthy controls, TBI patients had reductions in both the percentage and the absolute number of NK cells. Furthermore, the magnitude of NK cell reduction correlated with the degree of TBI severity at several time points. That is, NK cell population size was independently associated with lower Glasgow Coma Scale scores. In addition, at some time points, a positive correlation was found between the NK cell counts and Glasgow Outcome Scale scores. Our results indicate that TBI induces a reduction in the number of NK cells, and the magnitude of the reduction appears to parallel the severity of TBI. To investigate the relationship between natural killer (NK) cells and traumatic brain injury (TBI), we tracked an established phenotype of circulating NK cells at several time points in patients with different grades of TBI. In serial peripheral blood samples, NK cells were prospectively measured by flow cytometry of CD3-CD56 + lymphocytes. Compared to the healthy controls, TBI patients had reductions in both the percentage and the absolute number of NK cells. Furthermore, the magnitude of NK cell reduction correlated with the degree of TBI severity at several time points That is, NK cell population size was independently associated with lower Glasgow Coma Scale scores. In addition, at some time points, a positive correlation was found between the NK cell counts and Glasgow Outcome Scale scores. Our results indicate that TBI induces a reduction in the number of NK cells, and the magnitude of the reduction appears to parallel the severity of TBI.