At high altitudes, the clinically defined respiratory disturbance index (RDI) and high hypoxic ventilatory response (HVR) have been associated with diminished sleep quality. Increased RDI has also been observed in some athletes sleeping at simulated moderate altitude. In this study, we investigated relationships between the HVR of 14 trained male endurance cyclists with variable RDI and sleep quality responses to simulated moderate altitude. Blood oxygen saturation (SpO2%), heart rate, RDI, arousal rate, awakenings, sleep efficiency, rapid eye movement (REM) sleep, non-REM sleep stages 1, 2 and slow wave sleep as percentages of total sleep time (%TST) were measured for two nights at normoxia of 600 m and one night at a simulated altitude of 2,650 m. HVR and RDI were not significantly correlated with sleep stage, arousal rate or awakening response to nocturnal simulated altitude. SpO2 was inversely correlated with total RDI (r = -0.69, P = 0.004) at simulated altitude and with the change in arousal rate from normoxia (r = -0.65, P = 0.02). REM sleep response to simulated altitude correlated with the change, relative to normoxia, in arousal (r = -0.63, P = 0.04) and heart rate (r = -0.61, P = 0.04). When stratified, those athletes at altitude with RDI >20 h(-1) (n = 4) and those with <10 h(-1) (n = 10) exhibited no difference in HVR but the former had larger falls in SpO2 (P = 0.05) and more arousals (P = 0.03). Neither RDI (without stratification) nor HVR were sufficiently sensitive to explain any deterioration in REM sleep or arousal increase. However, the stratified RDI provides a basis for determining potential sleep disturbance in athletes at simulated moderate altitude.