OBJECTIVE The objective of our study was to describe the results from human experiments during normoxia that demonstrate the effect of pulsating arteries on the measured arterial oxygen saturation (SpO2) using a reflectance pulse oximeter sensor. METHODS In 6 healthy adults and 7 healthy neonates, a Nellcor reflection sensor (FS-10 oxisensor, Nellcor, Inc., Pleasanton, CA) was placed in three different positions: (1) on the forehead, (2) on the temporal area, with the photodiode placed over the superficial temporal artery, and (3) on the temporal area, with the light-emitting diodes (LEDs) placed over the superficial temporal artery. RESULTS Placement of the sensor in position 2 resulted in a significantly lower SpO2 reading, compared to sensor position 1: 5.8% (p < 0.01) lower for adults and 7.5% (p < 0.01) lower for neonates. Placement of the sensor in position 3 resulted in significantly larger plethysmographic signals, compared to sensor position 1; but, the Spo2 readings were alike. CONCLUSIONS Pulsating arteries can affect the reliability of reflection pulse oximetry. Depending on the position of the sensor, a falsely low Spo2 value can be observed.