This study aimed to compare changes in biomarkers of nutrient metabolism, thyroid hormones and oxidative stress parameters present during the early (EL) and mid-lactation (ML) stages in dairy cows reared under the hot summer conditions at Assiut city, Upper Egypt. Blood serum of twenty nine multiparous clinically healthy lactating Holstein Fresien cows (16 early lactating and 13 mid lactating cows) belonged to a private farm located under the same temperatures and living conditions were used in this study.Cows of ML had significantly lower values (P < 0.05) than those of EL stage for glucose and cholesterol concentrations and also non-significantly differences in total protein, albumin and triglycerides (P>0.05). Similarly, non-significance differences (P> 0.05) were found between the two lactation stages for thyroid hormones (Triiodothyronine, Thyroxine). For oxidants/antioxidant parameters, ML cows had significantly decreased values (P<0.05) for Superoxide dismutase and significantly increased values (P<0.05) for Glutathione S- Transfereas activities than those of EL as well as non-significantly differences (P>0.05) for Malondialdehyde concentrations and catalase activity. Pearson's correlation coefficients between the metabolic parameters, thyroid hormones and oxidative indices in early and mid-stages of lactation showed different positive and also negative correlations. Can be concluded that this study gives evidence that the lactating cows undergo a substantial oxidative stress that related to metabolic and physiological adaptation during early lactation to mid lactation stages under the under the influence of high temperature conditions at Upper Egypt.