Background: The neuropeptide (tachykinin) substance P is widely distributed in the central and peripheral nervous systems. Substance P has been suggested to function as a neurotransmitter, cotransmitter, or neuromodulator in the central and peripheral nervous system. substance P also influences sleep physiology. Neurokinin 1 (NK-1) receptors may also be implicated in the control of sleep/wake behavior. Obstructive sleep apnea syndrome (OSAS) is defined as repeated episodes of upper airway occlusion during sleep with subsequent excessive daytime sleepiness (EDS). Subsatance P levels are found to be significantly lowered in patients with OSAS. Objective: The aim of this review was to investigate the relationship between substance P, EDS and other OSAS complications. Methods: The literature was searched using standard methods. Medline and Embase were searched systematically from 1974 to the end of February 2008 for relevant articles published in English. Results/conclusion: EDS seen in some OSAS patients may be associated with various pathophysiological mechanisms including changes in substance P levels. Intravenous substance P administration in OSAS patients can be effective in the treatment of EDS. Further studies on the possible relationship between low serum substance P and hypertension, reproductive function disorders, memory and learning problems in OSAS cases is required.