Key points Recent evidence indicates a role for group III/IV muscle afferents in reflex control of the human ventilatory response to exercise. Dyspnoea in chronic obstructive pulmonary disease (COPD) may be linked to this reflex response. This study shows that activation of the muscle metaboreflex causes a ventilatory response in COPD patients but not in healthy controls. This indicates abnormal involvement of muscle afferents in the control of ventilation in COPD which may be a contributing factor to exercise dyspnoea. Abstract Blockade of thin fibre muscle afferent feedback during dynamic exercise reduces exercise hyperpnoea in health and chronic obstructive pulmonary disease (COPD). Therefore, we hypothesised that activation of the muscle metaboreflex at rest would cause hyperpnoea. We evaluated the effect of muscle metaboreflex activation on ventilation, in resting COPD patients and healthy participants. Following a bout of rhythmic hand grip exercise, post exercise circulatory occlusion (PECO) was applied to the resting forearm to sustain activation of the muscle metaboreflex, in 18 COPD patients (FEV1/FVC ratio < 70%), 9 also classified as chronically hypercapnic, and 9 age‐ and gender‐matched controls. The cardiovascular response to exercise and the sustained blood pressure elevation during PECO was similar in patients and controls. During exercise ventilation increased by 6.64 ± 0.84 in controls and significantly (P < 0.05) more, 8.38 ± 0.81 l min−1, in patients. During PECO it fell to baseline levels in controls but remained significantly (P < 0.05) elevated by 2.78 ± 0.51 l min−1 in patients until release of circulatory occlusion, with no significant difference in responses between patient groups. Muscle metaboreflex activation causes increased ventilation in COPD patients but not in healthy participants. Chronic hypercapnia in COPD patients does not exaggerate this response. The muscle metaboreflex appears to be abnormally involved in the control of ventilation in COPD and may be a contributing factor to exercise dyspnoea.