Obstructive sleep apnea (OSA) and sleep-disordered breathing have been implicated in the progression of cardiovascular disease and with increased risk of coronary artery disease, congestive heart failure, and stroke. Fractional flow reserve (FFR) is used to evaluate the physiological significance of coronary artery stenosis, and this technique is largely thought to be independent of systemic hemodynamic changes. Herein, we describe a case of OSA and sleep-disordered breathing cyclically altering FFR measurements from normal to abnormal in a patient with coronary artery disease. More specifically, we show that the abnormal FFR across a coronary lesion in a patient with sleep disordered apnea improves (to a normal threshold) with the initiation of continuous positive airway pressure (CPAP). This finding may have implications for the mechanisms of cardiac dysfunction in patients with OSA.