Increasingly we are monitoring the distribution of oxygen through the microcirculation using optical techniques such as optical reflectance spectroscopy (ORS) and near infrared spectroscopy. Mean blood saturation (S_mbO₂) and Tissue Oxygenation Index (TOI) measured by these two techniques respectively evoke a concept of the measurement of oxygen delivery to tissue. This study aims to establish whether S_mbO₂ is an appropriate indicator of tissue oxygenation. Spontaneous fluctuations in S_mbO₂ observed as changes in concentration of oxyhaemoglobin [HbO₂] and deoxyhaemoglobin [Hb] were measured by ORS in the skin microcirculation of 30 healthy subjects (15 male, age 21-42 years). Fourier analysis identified two distinctly different spontaneous falls in S_mbO₂. The first type of swing, thought to be induced by fluctuations in arterial blood volume, resulted from the effects of respiration, endothelial, sympathetic and myogenic activity. There was no apparent change in [Hb]. In contrast, a second type of swing resulted from a fall in [HbO₂] accompanied by a rise in [Hb] and was only induced by endothelial and sympathetic activity. Thus the same fall in S_mbO₂ can be induced by two distinct responses. A "type I" swing does not suggest an inadequacy in oxygen delivery whilst a "type II" swing may indicate a change in oxygen delivery from blood to tissue. Mean blood oxygen saturation alone cannot therefore be accepted as a definitive marker of tissue oxygenation.