Excessive erythrocytosis (EE; Hct ≥ 63% in men) is the hallmark of Monge?s disease or Chronic Mountain Sickness (CMS), a debilitating syndrome with high prevalence in Andean highlanders. EE is associated with typical CMS neurological symptoms and increased cardiovascular risk. Although largely impractical, common treatment includes the relocation of individuals to lower altitudes, or periodic bloodletting and hemodilution. We have shown that, unlike sedentary residents at the same altitude, high-altitude (HA) athletes maintain Hct values within sea-level range. Thus, we hypothesize that aerobic training is associated with lower Hct levels and might reduce EE. Therefore, this study aimed to investigate the effect of 8-week sub-maximal aerobic exercise training on Hct and CMS symptoms. Eight HA native men (40.9 ± 4.0 y) from Cerro de Pasco-Peru (4340 m) with CMS (Hct: 70.6 ± 1.9 %, CMS score: 8.8 ± 1.4) participated in the study. Clinical examination included questionnaires, spirometry, and ECG. Physiological measurements at baseline included Hct, arterial O2 saturation as measured by pulse oximetry (SpO2), heart rate (HR), blood pressure (BP), and a maximal exercise test to determine ventilatory parameters and peak VO2. 24h BP was measured by ambulatory BP monitoring (ABPM). Blood samples were collected for full blood cardiometabolic (CM) profiling and haptoglobin determination as a hemolysis marker. CMS score was assessed to determine the severity of the syndrome. All measurements were repeated after 4 and 8 weeks of exercise training. Sub-maximal aerobic work consisted of pedaling-exercise in a cycle-ergometer at 60% of peak VO2 for 1h/day, 4 days/week for 8 weeks. After 4 weeks, a maximal exercise test was repeated to readjust 60% of peak VO2 for the following 4 weeks. Hct decreased significantly by 5% and 7% (p<0.05) at weeks 4 and 8, respectively, while CMS score also showed a significant reduction to 4.8 ± 1.3 and 3.5 ± 0.8, respectively (p<0.05). SpO2 and ventilatory parameters at rest did not show significant differences either after 4 or 8 weeks. Similarly, CM blood markers, BP, and ABPM parameters showed no differences. Haptoglobin concentration showed an inverse correlation with Hct (r=?0.72, p<0.05) at baseline, and a significant decrease by week 8. Peak VO2 increased after 8 weeks (33.8 ± 2.4 vs. 37.2 ± 2.0 ml/min/kg, p<0.05), and maximum baseline workload (172.5 ± 9.4 W) also increased significantly at week 4 and 8 (198.9 ± 9.7 and 210.0 ± 27.8 W, p<0.01; respectively). Peak pulmonary ventilation showed an increase at week 8 (2.1 ± 0.4 vs 1.9 ± 0.5 l/min/kg, p<0.05) similarly to baseline maximal HR (153.3 ± 8.0 vs 169.5 ± 5.8 bpm, p<0.01). Our results show that reduction of Hct and CMS symptoms are not associated with an improvement in ventilatory management or oxygenation but rather to an increased training-induced workload as a consequence of increased physical performance. The inverse association of Hct and haptoglobin concentration at baseline, and higher serum haptoglobin values after 8 weeks, suggest that Hct reduction is most possibly related to increased hemolysis. In conclusion, regular exercise training might be used as a low-cost, practical treatment strategy for CMS.