Background: Despite therapeutic advances, chronic heart failure (CHF)-related mortality and hospitalization is still unacceptably high. Evidence shows that muscular wasting, sarcopenia, cachexia are independent predictors of mortality and morbidity in CHF and are signs of protein metabolism disarrangement (PMD), which involve all body proteins including circulating one. We postulate that circulating human serum albumin (HSA) could be a marker of PMD and catabolic low-grade inflammation (LGI) in CHF patients. Methods: One hundred sixty-six stable CHF patients (73% males), with optimized therapy referred to cardiac rehabilitation, were retrospectively divided into three groups based on their HSA concentration: =3.5 g/dL (normal value), 3.2-3.49 g/dL (low value); =3.19 g/dL (severe value). Hematochemical analyses (including circulating proteins and inflammatory markers) and body mass composition (by Bioelectrical Impedance Vector Analysis) were collected and compared. Correlations and multivariate regression were performed. Results: Despite being overweight (BMI=27 kg/m2), 75% of patients had reduced HSA (<3.5 g/dL) with suspectable sarcopenia, and 35% of all patients had remarkably lower albumin concentrations (<3.19 g/dL). Hypoalbuminemic patients were disable, older, with reduced muscular proteins, bilirubin and hemoglobin, increased extracellular water and LGI (P<0.01). HSA correlated with all of these parameters (all: P<0.01). Age, LGI, BMI, free-fat Mass, and bilirubin were independent predictors of HSA concentration. All these findings were male-dependent. Conclusions: HSA could be considered a simple marker of PMD and LGI in CHF patients. Evaluation of PMD and gender differences should be considered in new CHF clinical trials. © 2019 Edizioni Minerva Medica.