Hypoxemia is defined as abnormally reduced oxygenation of the blood, whereas tissue hypoxia indicates inadequate oxygen supply against oxygen demand in the integrity of cellular metabolic processes. Thus, the presence of tissue hypoxia may not be predicted by the level of hypoxemia alone. Obstructive sleep apnea syndrome is characterized by periodic apnea/hypopnea, which is often associated with severe hypoxemia. In this chapter, we discussed how tissue hypoxia should be assessed in this syndrome, and also what is the clinical usefulness and/or limitations of such assessment.