Background The mechanism of persistent neurohormonal and cardiorespiratory reflex abnormalities in chronic heart failure remain unclear. Also, why chronic heart failure patients who develop cachexia demonstrate a particularly abnormal neurohormonal profile and have a high risk of death is not known. Impaired reflex control within the cardiac and respiratory systems, and abnormal heart rate variability have both been linked to a poor outcome. Muscle reflexes may contribute to persistent neurohormonal overactivity in wasted patients. Thus, we hypothesized that patients with cardiac cachexia might exhibit particularly profound abnormalities in cardiorespiratory reflexes and heart ratevariability. Methods and Results We investigated 39 chronic heart failure patients: 13 with cardiac cachexia (non-intentional, non-oedematous, documented weight loss of >7·5% of previous normal weight over more than 6 months), and 26 non-cachectic chronic heart failure patients matched according to the severity of chronic heart failure (all men, mean age: 59 vs 60 years, NYHA functional class: 2·6 vs 2·5, peak O2consumption: 16·2 vs 16·8ml.kg−1.min−1, left ventricular ejection fraction: 23 vs 24%, all P>0·2 for cachectic vs non-cachectic). In the assessment of the cardiorespiratory reflex control we investigated: cardiac sympathovagal balance (using spectral analysis of heart rate variability to derive low (LF, 0·04–0·15Hz) and high frequency (HF, 0·15–0·4Hz) components), baroreflex sensitivity (using the phenylephrine method), and peripheral chemosensitivity (using the transient hypoxic method). There was a severely abnormal pattern of cardiorespiratory reflex control in patients with cachexia compared with non-cachectic patients. The former group exhibited severely impaired autonomic reflex control, characterized by an abnormal profile of heart rate variability (reduced LF component), and depressed baroreflex sensitivity (P=0·0001 and P=0·02, respectively, vs non-cachectics). Patients with cachexia also demonstrated an increased peripheral chemosensitivity (0·91 vs0·46l.min−1. %SaO2−1,P Conclusions Chronic heart failure patients who developed cardiac cachexia demonstrate an abnormal reflex control within the cardiovascular and respiratory systems. The nature of the link between this phenomenon and hormonal changes and the poor prognosis of cachectic chronic heart failure patients warrants further investigation.