There is a systematic relationship between fatigue, sleep, and decreased quality of life in cancer patients, with notably poor sleep quality among many head and neck cancer patients during and after treatment. An often overlooked cause of sleep disturbance in this patient population is obstructive sleep apnea (OSA). This review explores the current literature on the prevalence and clinical correlates of OSA, management outcomes, and data on cytokine-mediated fatigue in OSA. OSA appears to be prevalent in head and neck cancer patients, both at baseline and after treatment, especially with multimodality therapy including radiation therapy. Predictors of developing OSA include larger tumor size and hypopharynx or larynx primary site. There is evidence that the level of fatigue seen in these patients is not necessarily correlated with the severity of their OSA. Current research highlights the role of proinflammatory cytokines, which can also be synergistically activated by radiation therapy, as mediators of fatigue. Primary management of OSA consists of continuous positive airway pressure. Although continuous positive airway pressure has been shown to improve clinical symptoms, compliance with its use remains a problem and will be an area of future research.