Recent studies suggest that reactive oxygen species (ROS) function as second messengers in a variety of physiological processes. Reflexes arising from carotid body (CB) chemoreceptors play critical roles in the pathophysiology associated with chronic intermittent hypoxia (IH) caused by recurrent apnoeas. In the present study, we examined the potential importance of ROS in O2 sensing of the CB in a rodent model of IH. Chronic IH elicited selective augmentation of hypoxic sensory response and induced a novel form of functional plasticity manifested as sensory long-term facilitation (LTF). Systemic administration of membrane permeable superoxide dismutase (SOD) mimetic prevented chronic IH-induced changes in the CB activity. H2O2 at nanomolar concentration mimicked the effects of chronic IH on CB activity in normoxic animals. ROS levels in the carotid body were elevated in chronic IH exposed animals. Inhibition of complex I of the mitochondrial electron transport chain contribute in part to the increased generation of ROS. Chronic IH facilitated serotonin (5-HT) release by acute hypoxia via ROS dependent mechanisms, and 5-HT receptor antagonist prevented alterations in CB activity induced by chronic IH. These observations suggest that chronic IH facilitates O2 sensing in the CB by mechanisms involving increased generation of ROS in the chemoreceptor tissue.