Ball game players frequently perform changes of direction (CODs) while running; however, there has been little research on the physiological impact of CODs. In particular, the effect of running velocity on the physiological and energy demands of CODs while running has not been clearly determined. The purpose of this study was to examine the relationship between running velocity and the energy cost of a 180°COD and to quantify the energy cost of a 180°COD. Nine male university students (aged 18-22 years) participated in the study. Five shuttle trials were performed in which the subjects were required to run at different velocities (3, 4, 5, 6, 7, and 8 km/h). Each trial consisted of four stages with different turn frequencies (13, 18, 24 and 30 per minute), and each stage lasted 3 minutes. Oxygen consumption was measured during the trial. The energy cost of a COD significantly increased with running velocity (except between 7 and 8 km/h, p = 0.110). The relationship between running velocity and the energy cost of a 180°COD is best represented by a quadratic function (y = -0.012+0.066x +0.008x(2), [r = 0.994, p = 0.001]), but is also well represented by a linear (y = -0.228+0.152x, [r = 0.991, p<0.001]). These data suggest that even low running velocities have relatively high physiological demands if the COD frequency increases, and that running velocities affect the physiological demands of CODs. These results also showed that the energy expenditure of COD can be evaluated using only two data points. These results may be useful for estimating the energy expenditure of players during a match and designing shuttle exercise training programs.