A new method to non-invasively measure the absolute tissue oxygen saturation (SO2) and arterial oxygen saturation (fdSaO2) by frequency-domain spectroscopy is described. This method is based on the quantitative measurement of the tissue absorption spectrum, which is used to determine global SO2. From the amplitude of absorption changes caused by arterial pulsation oscillations, in the range of 633-841 nm, the fdSaO2 can be calculated. During deoxygenation (air/N2 mixture) experiments, we measured the fdSaO2 and SO2 on the forehead of three healthy volunteers and compared them to the arterial oxygen saturation measured by conventional pulse oximetry (poSaO2) on the finger. fdSaO2 and poSaO2 agree very well (mean difference: -1.2 +/- 2.6%). Changes in SO2 were systematically smaller than in fdSaO2 or poSaO2 probably due to autoregulation. The measurements with 4 and 8 wavelengths had comparable quality.