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Background  Maximum oxygen uptake is an established measurement of diagnosing chronic heart failure and underlies various central and peripheral factors. However, central and peripheral factors are little investigated, because they are usually measured invasively. The aim of this study was to compare non-invasively measured central and peripheral factors of oxygen uptake between patients with chronic heart failure and healthy controls.    Methods  Ten male patients with heart failure with reduced ejection fraction (62 ± 4 years; body mass index: 27.7 ± 1.8 kg/m 2 ; ejection fraction: 30 ± 4%) and ten male healthy controls (59 ± 3 years; body mass index: 27.7 ± 1.3 kg/m 2 ) were tested for blood pressure, heart rate, stroke volume, cardiac output, and cardiac power output (central factors) as well as muscle oxygen saturation of the vastus lateralis and biceps brachii muscle (peripheral factors) during an incremental cycling test. Stroke volume and muscle oxygen saturation were non-invasively measured by a bioreactance analysis and near-infrared spectroscopy, respectively. Additionally, a maximum isometric strength test of the knee extensors was conducted. Magnitude-based inferences were computed for statistical analyses.    Results  Patients had a likely to most likely lower oxygen uptake, mean arterial pressure, and heart rate at maximum load as well as very likely lower isometric peak torque. Contrary, patients had a possibly to likely higher stroke volume and muscle oxygen saturation of the vastus lateralis muscle at maximum load. Differences in cardiac output, cardiac power output, and muscle oxygen saturation of the biceps brachii muscle at maximum load were unclear.    Conclusions  Non-invasively measured central and peripheral factors of oxygen uptake differ between patients with chronic heart failure and healthy controls. Therefore, it is promising to measure both types of factors in patients with chronic heart failure to optimize the diagnosis and therapy.