The purpose of this study was to investigate the physiological responses to static muscle contractions in the standing position and the supine position. Eight subjects performed static contractions of the ankle extensors in both positions. Blood pressure (SBP and DBP), heart rate (HR), electromyography (EMG), and near-infrared spectroscopy (NIRS) were determined during the static contractions. The results of main interest were a significantly larger initial decline of muscle oxygen concentration and a steeper negative slope of the frequency content in the EMG signals in the supine position. These results indicate that the fatigue development is more pronounced in a supine position, which is most likely due to changes in muscle blood flow.