Background: Near-infrared spectroscopy (NIRS) technology can evaluate muscle metabolism and oxygenation. NIRS-based oximeters can measure skeletal muscle oxygen delivery and utilization during static and dynamic work non-invasively. Our goal was to assess the value and usability of NIRS technology in chronic obstructive pulmonary disease (COPD) rehabilitation program. Methods: Forty patients with COPD participated in a 4-week inpatient rehabilitation program that included breathing exercises and personalized cycle/treadmill training adjusted to the functional capacity, physical activity and comorbidities of the patients. A NIRS muscle oxygen monitor was used to measure tissue oxygenation and hemoglobin levels. Total hemoglobin index, average muscle oxygenation, minimal and maximal muscle oxygenation were recorded before and after the rehabilitation program. Results: Rehabilitation resulted improvement in 6 min walking distance (6MWD:335.3 +- 110. vs. 398.3 +- 126.2 m; P < 0.01), maximal inspiratory pressure (MIP: 57.7 +- 22.7 vs. 63.6 +- 18.0 cmH2O; P < 0.01), chest wall expansion (CWE: 2.84 +- 1.26 vs, 4.00 +- 1.76 cm; P < 0.01), breath hold time (BHT: 25.8 +- 10.6 vs. 29.2 +- 11.6 s; P < 0.01) and grip strength (GS: 24.9 +- 11.9 vs. 27.0 +- 11.4 kg; P < 0.01). Quality of life improvement was monitored by COPD Assessment Test (CAT: 17.00 +- 8.49 vs. 11.89 +- 7.3, P < 0.05). Total hemoglobin index (tHb: 12.8 +- 1.3% vs. 12.8 +- 1.4), average muscle oxygenation (SmO2: 67.5 +- 14.4% vs. 65.2 +- 20.4%) showed a tendency for improvement. Maximal muscle oxygenation decreased (SmO2 max: 98.0 +- 20.5% vs. 90.1 +- 14.3%; P < 0.01). Minimal muscle oxygenation increased (SmO2 min: 42.6 +- 12.6% vs. 54.8 +- 14.3%; P < 0.01). Conclusions: NIRS results showed that muscle oxygenation and microcirculation can be described as a high-risk factor in COPD patients. The 4-week rehabilitation improves functional parameters, quality of life and tissue oxygenation levels in COPD patients.