Endothelial dysfunction and exercising muscle underperfusion partecipate in causing exercise intolerance, hyperventilation and breathlessness in atrial fibrillation (AF). Cardioversion (CV) improves endothelial function and exercise performance. We examined whether CV is equally benefical in diabetes and hypertension, diseases that cause endothelial dysfunction and are often associated with AF. Cardiopulmonary exercise, pulmonary and endothelial (brachial artery flow-mediated dilatation, FMD) function, were tested before and after CV, in patients with AF, either lone (18, group 1) or associated with hypertension (19, group 2) or diabetes (19, group 3). Compared with group 1, peak exercise workload, oxygen consumption (VO₂), oxygen pulse (O₂ pulse), aerobic efficiency (VO₂/WR), and ratio of brachial diameter changes to flow changes (D/F) were reduced in group 2 and to a greater extent in group 3; exercise ventilation efficiency (VE/VCO₂ slope) and dead space to tidal volume ratio (VD/VT) were similar among groups. CV was less effective in group 2 than in group 1 on peak workload (+7% vs +18%), peak VO₂ (+12% vs+17%), O₂ pulse (+33% vs+50%), VO₂/WR (+7% vs +12%), VE/VCO₂ slope (-6% vs -12%), D/F (+7% vs +10%) and breathlessness (Borg scale), and was ineffective in group 3. The antioxidant vitamin C, tested in 8 additional patients in each cohort, improved FMD in groups 1 and 2 before and not after CV, and was ineffective in group 3, suggesting the possibility that the oxidative injury is least in lone AF, greater in hypertension with AF and greater still in diabetes with AF. Comorbidities that impair endothelial activity, worsen endothelial dysfunction and exercise intolerance in AF. With respect to our data, advantages of CV appear to be inversely related with the extension of the underlying oxidative injury.