Patients with heart failure and sleep apnea have greater chemoreflex sensitivity, presumably due to intermittent hypoxia (IH), and this is predictive of mortality. We hypothesized that endurance training would attenuate the effect of IH on peripheral chemoreflex sensitivity in healthy humans. Fifteen young healthy subjects (9 female, 26 ± 1 years) participated. Between visits, 11 subjects underwent eight weeks of endurance training that included running four times/week at 80% predicted max heart rate and interval training, and 4 control subjects did not change activity. Chemoreflex sensitivity (the slope of ventilation responses to serial oxygen desaturations), blood pressure, heart rate, and muscle sympathetic nerve activity (MSNA) were assessed before and after 30 minutes of IH. Endurance training decreased resting systolic blood pressure (119 ± 3 to 113 ± 3 mmHg, P = 0.027) and heart rate (67 ± 3 to 61 ± 2 beats/minute, P = 0.004), but did not alter respiratory parameters at rest (P > 0.2). Endurance training attenuated the IH-induced increase in chemoreflex sensitivity (pre-training: 0.045 ± 0.026 vs. post-training: - 0.028 ± 0.040 L/min/%O₂ desaturation, P = 0.045). Furthermore, IH increased mean blood pressure and MSNA burst rate before training (P < 0.05), but IH did not alter these measures after training (P > 0.2). All measurements were similar in the control subjects at both visits (P > 0.05). Endurance training attenuates chemoreflex sensitization to IH, which may partially explain the beneficial effects of exercise training in patients with cardiovascular disease.