Abstract Background: Heart failure (HF) is characterised by reduced tolerance to effort, associated with progressive fatigue and dyspnoea. Neuro-hormonal activation is a hallmark of HF and influences its clinical evolution. Aim: To evaluate the relationship between neuro-hormonal activation, exercise capacity and ventilatory efficiency. Methods and results: 154 HF patients (127 males, 62±1 years) underwent cardiopulmonary exercise testing and resting blood sampling for assay of plasma brain natriuretic peptide (BNP), NT-proBNP, norepinephrine, epinephrine, aldosterone and plasma renin activity (PRA). BNP and NT-proBNP levels correlated with peak oxygen consumption (VO2) (both R=−0.53, p<0.001), VE/VCO2 slope (R=0.56; p<0.001 and R=0.58; p<0.001, respectively) and maximum workload (R=−0.49; p<0.001 and R=−0.47; p<0.001, respectively). Norepinephrine correlated slightly less with peak VO2 (R=−0.38, p<0.001), VE/VCO2 (R=0.45; p<0.001) and maximum workload (R=−0.35; p<0.001). There was a significant inverse correlation between left ventricular ejection fraction and BNP (R=−0.48, p<0.001), NT-proBNP (R=−0.42; p<0.001) and norepinephrine (R=−0.43; p<0.001). Weaker correlations were found for PRA, exercise parameters and ejection fraction. ROC curves showed that BNP was able to identify patients with peak VO2<14 ml/min/kg (cut-off 98 pg/ml, AUC 0.775) and a VE/VCO2>35 (cut-off 183 pg/ml, AUC 0.797), as well as NT-proBNP (cut-off 537 pg/ml, AUC 0.799 and cut-off 1010 pg/ml, AUC 0.768, respectively) and norepinephrine (cut-off 454 pg/ml, AUC 0.716 and cut-off 575 pg/ml, AUC 0.783, respectively). Conclusion: Haemodynamic impairment (as indicated by BNP and NT-proBNP plasma values) and sympathetic activation predict exercise capacity and ventilatory efficiency in HF patients.