Despite the documented health benefits of physical activity, the mechanism whereby physical activity prevents cardiovascular disease is incompletely understood. In the present study, we investigated the relationship between white blood cell (WBC) count and cardiorespiratory fitness (V o(2)max) after adjusting for several well-known cardiovascular risk factors. Subjects who visited our health promotion center for a medical checkup and treadmill test (n=8241; age: median, 48 years; range, 16-79 years) were classified into 3 groups based on their WBC counts (group 1, 2200-5300 microL, n=2823; group 2, 5301-6500 microL, n=2709; group 3, 6501-10000 microL, n=2709). After adjusting for age, body mass index, body fat percentage, smoking history, systolic blood pressure, diastolic blood pressure, serum lipid profile, and fasting plasma glucose, V o(2)max still showed a significant association with WBC count (partial r=-0.11, P<.001). In logistic regression analyses, subjects in the highest WBC tertile showed lower V o(2)max compared with those in the lowest WBC tertile after adjusting for age and cardiovascular risk factors (odds ratio, 0.42; 95% confidence interval, 0.36-0.49 for the highest V o(2)max tertile). These results suggest that a WBC count in the normal concentration range is independently related to cardiorespiratory fitness in Korean men.