The cardiovascular system is one of the most critical animal systems. Its main functions are to supply organs and tissues with oxygen and nutrients and to remove metabolic products from tissues. Diseases of the cardiovascular system of animals cause significant economic damage, including reduced productivity, reproductive qualities, and the development of concomitant diseases. The prevention, diagnosis, surgery, and treatment of such pathologies are only possible by knowing the morphofunctional parameters of comparative anatomy, histology, and physiology. The heart plays a vital role in blood circulation and regulates the proper functioning and development of all organs of animal and human organisms. The study of the heart structure reveals topography features, age-related morphology, and development of this organ in domestic animals and remains relevant. The article is a fragment of the scientific developments of the Department of Normal and Pathological Morphology, Hygiene and Forensics of Polissia National University on the following topics: “Features of the morphology of the heart of domestic mammals” (state registration number 0121U108884); “Development, morphology and histochemistry of animal organs in normal and pathological conditions”, state registration number 0113U000900. In the study, sexually mature clinically healthy animals (n = 5) belonging to the class Mammalia – Mammals, species Ovis aries L., 1758 – domestic sheep (ram) were investigated. The study aimed to evaluate the morphological structures of the heart of mature sheep using macro- and microscopic, morphometric, and statistical research methods. The heart of a sexually mature domestic sheep was subjected to anatomical dissection. Sections were stained with hematoxylin and eosin to study the cyto- and histoarchitectonics of the heart for microscopic examination of transverse striated myocardial muscle tissue, detection of cardiomyocyte cytostructure, and Heidenhain staining of histological specimens were used. The morphology of the heart in sheep has a similar organization plan, topographic location of the organ, and anatomical and histological structure. However, there are some striking species and morphological features. The heart of the domestic sheep belongs to the expanded-shortened anatomical type (according to its development index – 145.5 ± 4.02 %). According to the studies, the absolute and relative weight of the heart of mature sheep is, accordingly, 208.4 ± 9.82 g and 0.44 ± 0.007 %, and the weight without epicardial fat is 175.0 ± 8.17 g. It has been shown that the microscopic structure of the ventricles and atria of the sheep heart differ in cytometric parameters. Cardiomyocytes of the left ventricle have the most significant volume (3982.99 ± 423.96 μm3), the smaller – of the right ventricle (2463.02 ± 318.04 μm3). The lowest index was observed in atrial cardiomyocytes (1215.93 ± 176.94 μm3). The volumes of cardiomyocyte nuclei in the left ventricle were (53.42 ± 5.18 μm3) and in the right ventricle (52.85 ± 4.33 μm3). The volume of atrial nuclei (50.16 ± 4.57 μm3) is almost the same. Such ambiguous morphometric parameters of cardiomyocytes and their nuclei volumes are directly reflected in their nuclear-cytoplasmic ratio, which is the smallest in cardiomyocytes of the left ventricle (0.0136 ± 0.0062), larger in cardiomyocytes of the right ventricle (0.0219 ± 0.0079) and the largest (0.0430 ± 0.0096) in atrial cardiomyocytes. The obtained results of the study of the macro- and microscopic structure of the heart of domestic sheep significantly supplement the information on heart morphology in the relevant sections of comparative anatomy and histology and are a significant contribution to clinical cardiology.