Background Cardiac myofibrillary dysfunction, which can be measure by echocardiographical strain value, represents an early subclinical manifestation of heart failure. Epicardial Adipose tissue (EAT) is related to low degree inflammation and oxidative damage in the adjacent tissue. Aim To explore whether EAT affects early myocardial dysfunction, as assessed strain values. Methods Case–Control design. Patients lacking clinical significant heart failure, thyroid or renal disease or malignant abnormalities were included. Clinical-demographic and biochemical data were collected. EAT and myofibril deformation were measured by echocardiography. Results A total of 71 patients were analyzed, and further subdivided according to type 2 Diabetes Mellitus (t2DM). Higher strain value (higher than -22.4%cut-off value) was associated with male sex and higher anthropometric and metabolic risk measures; particularly those with t2DM. Higher EAT was also associated higher strain value (AUC = 0.92 ± 0.06, p = 0.004), and further correlation was evidenced (rho = 0.488, p < 0.001), with significant influence of t2DM. Conclusion EAT was related to strain value, suggesting the influence of cardiac adipose tissue on the deformability of cardiac myofibril, with a more significant effect in the population with t2DM.