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Epicardial adipose tissue (EAT) deposition has a strong association with aspects of metabolic dysfunction, including obesity. The size of the EAT adipocytes in relation to obesity, however, has rarely been researched. Therefore, to contextualise EAT within the broader framework of pathophysiological adipocyte size changes in obesity, we aimed to determine whether EAT adipocyte size is associated with body mass index (BMI). During routine post-mortem examination, adipose tissue biopsies were obtained from four depots of 43 cases, including EAT, as well as pericardial (PAT), appendix mesenteric (AAT), and clavicular subcutaneous (SAT) adipose tissues. Tissues were fixed, sectioned, and stained using haematoxylin and eosin. The size (measured as area) of each adipocyte imaged from the depots was analysed in relation to BMI. Mean size of EAT adipocytes was significantly smaller than that from SAT and AAT depots, while not differing from PAT adipocytes. BMI positively correlated with the size of adipocytes isolated from SAT (r =0.5893, P <.0001), PAT (r =0.5854 , P <.0001), and AAT (r =0.5829 , P <.0001) depots, but not from EAT (r =0.1242 , P =.4274), even after multivariate adjustment for age and sex. EAT adipocyte size is not associated with increased BMI despite significant associations within adipocytes from other adipose depots. • Adipocyte hypertrophy underlies adipose tissue expansion in obesity. • Adipocytes from four adipose depots of 43 post-mortem cases were measured. • Epicardial adipocyte size did not correlate with body mass index. • Adipocytes from all other depots had significant positive size-BMI correlations. [ABSTRACT FROM AUTHOR]