The authors studied the leading indicators of the cholesterol profile of high-density lipoproteins (HDL-C), low-density lipoproteins (LDL-C) and total cholesterol (TC) in Black-and-White, Red Steppe and Holstein breeds of the second or third lactation, bred in large livestock farms—complexes on the territory of Western Siberia. Metabolism and concentration of lipid complexes of cholesterol status play a cardinal role in the homeostasis of cellular metabolic processes. The critical role of serum lipoproteins in cholesterol metabolism is well recognised, as is their role as predictors of cardiovascular disease. At the same time, the atherogenic effect of LRN-C is associated with the transfer of fatty acids, which act as energy substrates for ATP synthesis. Anti-atherogenic properties characterise HDL-C and have an antioxidant and anti-inflammatory effect. The concentration of HDL-C - was determined by the precipitation method of phosphotungstic acid with magnesium chloride; the level of LDL-C - by the enzymatic colourimetric direct method, total cholesterol - by the process of enzymatic hydrolysis and oxidation of CHOD-PAP using reagent kits “HDL-Cholesterol-Novo”, “LDLCholesterol-Novo-A”, “Cholesterol-Novo” (“Vector-Best, Russia. The content of OH and LDL-C in the blood serum of cows at the age of the second or third lactation bred in Western Siberia is higher than the generally accepted standard values, which reflects a different degree of adaptation to climatic conditions. Ranked series of breeds (p < 0.05) according to LDL-C: black-and-white → Holstein → red steppe, medians were 4.91; 2.77 and 2.24 mmol/l, respectively. Differences between the indicators of HDL-C and LDL-C in Black-and-White, Red Steppe and Holstein cows were established, which indicates the genetic determination of the level of lipoproteins in the blood serum. The strength of the influence of the cow breed factor on the level of HDL-C in blood serum was 29%, LDL-C - 17%.