Heart failure is a pathological condition characterized by cardiac dysfunction and neuroendocrine system activation. The aim of this study was to evaluate serum ??-1 proteins in the characterization of heart failure patients. The study included 69 patients with documented heart failure disease and 44 healthy individuals. We included 12 out of 69 patients with preserved (>50%) left ventricular ejection fraction. ??-1 protein levels were evaluated using routine capillary electrophoresis. Markers of inflammation, such as interleukin-6 (IL-6) and tumor necrosis factor-??, were measured with UltraSensitive ELISA Kits. C-reactive protein and brain natriuretic peptide were determined by automated assays. No difference in ??-1 protein levels between patients with reduced versus preserved left ventricular ejection fraction was observed. IL-6, tumor necrosis factor-??, and C-reactive protein concentrations were significantly increased in patients with respect to the control group (P???<0.001, P???<0.01, and P???<0.05, respectively). A progressive increase in ??-1 protein levels across NYHA classes (P???=???0.0077) was observed. Brain natriuretic peptide median value of the patient group was 287???ng/l (92-602???ng/l) and was significantly associated with ??-1 proteins and IL-6 levels (P???<0.05 and P???<0.01, respectively). Considering recent findings and our preliminary data, we hypothesized that the overexpression of ??-1 antitrypsin (AAT) protein (and probably elevated AAT levels) is a compensatory mechanism as a consequence of the loss of the antiprotease activity, induced by the increase of oxidative stress in heart failure patients. In conclusion, we assume that ??-1 proteins and AAT could contribute to the prognostic stratification of heart failure patients.