Weight loss is common in patients with chronic heart failure (CHF) and is associated with adverse outcome. Activation of the sympathetic nervous system has been implicated in weight loss, wasting and cachexia. However, the effect of sympathetic antagonism on weight change in patients with CHF is not well defined. We evaluated changes in body weight, the incidence of cachexia (weight loss >6%) and significant weight gain (>5%) in unselected patients with CHF due to left ventricular systolic dysfunction (LVSD) (LV ejection fraction (LVEF) <40%) and studied the effect of beta-blockade on weight change. Of the 1480 patients enrolled (median NTproBNP:1651 ng/L, median LVEF:31%), 86% received beta-blocker, 11% never had beta-blocker and 3% discontinued beta-blocker between baseline and 1 year. Patients who did not have or tolerate beta-blocker were more likely to develop cachexia (23% vs 10%, p < 0.001) and less likely to have significant weight gain (22% vs 24%, p < 0.001) than patient who had beta-blocker. During a median follow up of 1876 days (IQR: 993-3052 days), 894 (60%) patients died. Higher body mass index (BMI) at baseline, weight gain and beta-blocker therapy were associated with better outcome. Patients who had all 3 features: beta-blocker therapy, baseline BMI ≥ 25 and significant weight gain had the best outcome (22% mortality at 5 years). Patients with CHF due to LVSD who receive beta-blocker were less likely to develop cachexia and more likely to have significant weight gain and better outcome compared to patients who did not receive or tolerate beta-blocker.