The influence of skin on the bias and reproducibility of regional cerebral oxygenation measurements is investigated using cw near-infrared spectroscopy (NIRS). Receiving optodes are placed over the left and right hemispheres of a piglet (C3, C4 EEG placement code) and one transmitting optode centrally (Cz position). Optical densities (OD) are measured during stable normo, mild, and deep hypoxemia. This is done for skin condition 1: all optodes on the skin; skin condition 2: transmitting optode on the skin and one receiving optode on the skull; and skin condition 3: all optodes on the skull. Absolute changes of oxy- (cO2Hb), deoxyhemoglobin (cHHb), and total hemoglobin (ctHb) concentrations [micromolL] are calculated from the ODs. These absolute changes are calculated for each skin condition with respect to normoxic condition. Additionally, for skin condition 2, the difference of concentration changes between receiver 1 (skull) and receiver 2 (skin) is calculated. The effect of skin removal is an average increase of attenuation changes by a factor of 1.66 (=0.51 OD) and of the concentration changes due to the arterial oxygen saturation steps by 23\%. We conclude that skin significantly influences regional oxygenation measurements. Nevertheless, it is hypothesized that the estimated concentration changes are dominated by changes of the oxygenation in the brain.