The aim of the study was to examine concentrations and relationships between melatonin levels assessed at 0:200 hrs and 0:700 hrs, lipid hydroperoxide (LPO) assessed at 0:200 hrs and 0:700 hrs, and apolipoprotein (apo)AI, apoAII, apoB, high sensitivity C-reactive protein (hsCRP) and NT-proBNP, in 27 patients with chronic heart failure (CHF) (17 patients - with NYHA class II and 10 - with NYHA class III). In the study, Lipoproteins apoAI, apoAII, apoB, high sensitivity C-reactive protein (hsCRP) levels were determined by way of immunonephelometric methods, serum melatonin concentration was measured by using a competitive enzyme immunoassay technique, while serum LPO concentration was measured by using Cayman’s Lipid Hydroperoxide Assay Kit. In the study, CHF patients without acute inflammatory response demonstrated a decreased concentration of high density lipoprotein cholesterol (HDL-C), apoAI, apoAII levels, but an increased concentration of NT-proBNP, hsCRP and LPO at night, and LPO at daytime; however, the concentration of LPO at 0:700 was lower than at 0:200. Pearson’s correlation test and multiple ridge stepwise regression showed that melatonin administered at night exerts an effect on the composition of apoAI and apoAII of HDL particles, and induces decreased LPO at 0:700, but has no effect upon NT-proBNP levels in patients with NYHA class II. However, in patients with NYHA class III, melatonin administered at night induces an increase in the content of apoAII and apoAI, which further decreases hsCRP, and this, together with the administered melatonin, brings about daytime decreases in NT-proBNP and hsCRP levels. The results indicated that the content of apoAII and apoAI in HDL particles and melatonin demonstrate an anti-oxidative and anti-inflammatory effect, and together, have a cardio-protective effect on patients with advanced CHF. Hence, the results support melatonin being a cardio-protective agent. These relationships, however, need to be confirmed in further studies.