Aims: Heart failure with preserved (HFpEF) and mid-range ejection fraction (HFmrEF) are becoming the most prevalent forms of heart failure. Patients with HFpEF/HFmrEF in atrial fibrillation (AF) have poorer survival and quality of life, but the mechanism underpinning this is unknown. We sought to investigate the influence of AF on the haemodynamic profile of HFpEF/HFmrEF patients at rest and during exercise. Methods and results: We invasively measured central haemodynamics at rest and during symptom-limited supine bicycle exercise in HFpEF/HFmrEF patients, 35 in sinus rhythm and 20 in AF with matched left ventricular ejection fraction. At rest, AF patients had significantly increased pulmonary capillary wedge pressure, lower cardiac index and reduced left ventricular stroke work index, despite similar resting heart rate. Under resting conditions, calculated oxygen consumption and systemic arteriovenous oxygen gradient were not different between the two groups. During supine cycling at similar levels of workload, AF patients exhibited a reduced capacity to increase their oxygen consumption and this was accompanied by a persistently impaired cardiac index and left ventricular stroke work index. Conclusions: The adverse interaction of AF and HFpEF/HFmrEF may be accounted for by an adverse impact on left ventricular systolic function and peripheral oxygen kinetics.