Abstract: BACKGROUND: Epicardial fat thickness (EFT) in adults and children has been related to the metabolic syndrome and other cardiovascular risk factors; however, scarce studies have evaluated it in infants of diabetic mothers (IDM) in whom, alterations in the thickness of the interventricular septum have been reported. This study compares the EFT in IDM versus infants of non-diabetic mothers (INDM) and its association with others echocardiographic parameters. METHODS: We performed a cross sectional study in 93 infants (64 IDM and 29 INDM). To evaluate EFT dimensions, an echocardiogram was performed within the first 24h of extrauterine life in both groups. In diabetic mothers, HbA1c was also determined. RESULTS: There was no significant difference in birth weight between the groups although gestational age was lower in IDM. The EFT (3.6 vs. 2.5 mm, p < 0.0001), the interventricular septum thickness (IVST) (6.2 vs. 5.2 mm, p < 0.0001) and the IVST / left ventricle posterior wall (1.3 vs. 1.1, p = 0.001) were higher in the IDM; while the left ventricular expulsion fraction [LVFE] (71.1 vs. 77.8; p < 0.0001) was lower than in the INDM, respectively. We found a positive correlation between EFT with IVST (r = 0.577; p = 0.0001), LVPW (r = 0.262; p = 0.011), IVST/LVPW index (r = 0.353; p = 0.001), and mitral integral early velocity (r = 0.313; p = 0.002), while a negative correlation with LVFE was observed (r = –0.376; p = 0.0001). CONCLUSIONS: The EFT is higher in IDM than in INDM. It was positively related with echocardiographic parameters of left ventricular thickness and negatively with left ventricular ejection function.