Postpartum metabolic and inflammatory disorders, including ketosis, puerperal paresis, and mastitis, profoundly affect milk composition and have significant implications for dairy herd productivity and health. This study aimed to investigate breed-related differences in milk chemical composition between Holstein-Friesian and Simmental cows during early lactation prior to therapeutic intervention. A total of 360 cows were examined and grouped by disease and breed. Milk was analyzed for fat, protein, casein, lactose, solids-not-fat, fatty acid profiles (saturated, unsaturated, polyunsaturated), BHB, acetone, minerals (Ca, P, Mg), milk urea, citrate, somatic cell count, and pH (mastitis). ANOVA assessed breed differences, while correlation and regression analyses evaluated associations among metabolic markers and milk components. Chi-Square tests examined breed-specific differences within disease categories. Holstein-Friesian cows with ketosis showed higher BHB (450±30 μmol/L) and acetone (2.5±0.2 mmol/L) compared to Simmental (BHB 380±25 μmol/L; acetone 1.8±0.2 mmol/L; p<0.001), reflecting enhanced lipid mobilization. In mastitis, reductions in protein (Holstein 2.9±0.2% vs Simmental 3.0±0.2%; p<0.002) and lactose (4.0±0.1% vs 4.1±0.1%; p<0.001) were more pronounced in Holstein-Friesians. Puerperal paresis was associated with lower milk calcium (95±5 mg/100 mL vs 100±4 mg/100 mL; p<0.001), phosphorus, and magnesium in Holstein-Friesians. Regression models showed that BHB and acetone explained up to 72% of protein variation, while Chi-Square tests confirmed significant breed-specific metabolic differences. However, mechanistic explanations for breed differences remain unclear, and potential confounders such as diet, housing, and environmental factors were not fully controlled, limiting causal inference. These findings highlight milk composition as an integrated biomarker system for monitoring postpartum metabolic and inflammatory stress. Understanding breed-specific responses may inform targeted nutritional strategies, early detection, and precision herd management, enhancing both animal welfare and milk productivity.