Myocardial fibrosis is considered a key pathological process in the development of cardiovascular diseases. In epicardial obesity (EO), the main cause of fibrosis development is lipotoxic myocardial damage. It is important to detect myocardial fibrosis at an early stage, using non-invasive diagnostic methods. According to the results of echocardiography (ECG), 110 men with general obesity were divided into the following two groups: Group I with epicardial fat thickness (tEAT) ≥ 7 mm (n = 70) and Group II with tEAT < 7 mm (n = 40) without diastolic dysfunction. The levels of metabolic factors, pro-inflammatory cytokines, adipokines, and free fatty acids (FFA), profibrotic markers were determined in both groups. In Group I, the level of interleukin (IL)-6, C-reactive protein, and tumor necrosis factor (TNF)-α increased and that of leptin and adiponectin decreased compared with those in Group II. There was an increase in the level of all studied profibrotic factors in Group I. The level of TNF-α and IL-6 showed a positive correlation with the level of leptin and FFA and a negative correlation with the level of adiponectin. We also observed a relationship between the level of collagen, transforming growth factor (TGF)-β, and metalloproteinase (MMP)-3 and EO. Our results showed that confirmed EO correlates with not only disadipocytosis and increased levels of pro-inflammatory cytokines, but also increased levels of profibrotic factors. This suggests that the studied markers of fibrosis may be used to determine preclinical cardiac fibrosis with lipotoxic myocardial damage in patients with EO.