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Background and Aim: Biochemical blood testing is the main diagnostic indicator of the clinical condition of highly productive animals and a method of determining changes in metabolic disorders. This study focuses on metabolic changes (ketosis), which are of the utmost importance in the assessment of the health status of animals, as well as differences in intergroup characteristics. The main focus of this study is to demonstrate the influence of subclinical ketosis in highly productive cows on changes in biochemical blood parameters during different physiological periods to further prevent this disease, adjust feeding rations, and prevent premature culling of animals. This study aimed to evaluate and establish changes in the biochemical status dynamics of highly productive cows with metabolic disorders in an industrial livestock complex. Materials and Methods: Blood samples were systematically collected from highly productive cows of the Simmental breed (n = 60) and served as the primary material for subsequent analyses. Each methodological step was designed to ensure evaluation of the metabolic changes associated with post-calving adjustments in highly productive dairy cows. This study employed a comprehensive approach integrating clinical assessments, laboratory analyses, biochemical evaluations, instrumental measurements, and statistical analyses. Results: A biochemical blood test showed that the number of ketone bodies in the experimental group exceeded the norm, varied depending on the physiological state of the animals, and ranged from 0.89 to 1.45 mmol/L. At 10 days after calving, the highest indicator was 1.45 ± 0.05 mmol/L. This indicator was 1.05 mmol/L higher than that in the control group and exceeded the norm by 0.95. Conclusion: Excess ketone bodies in the blood of animals led to accumulation in urine and milk, indicating a disturbance in metabolic processes in the body and a decrease in the quality of animal husbandry products. The sample size and the focus on a single breed from one geographical location may limit the generalizability of the findings. Further research should explore the mechanistic bases of ketosis development, potentially integrating genomic and proteomic approaches to understand the genetic predispositions and molecular pathways involved.