This experiment was aimed to investigate the variations of serum nutritional status indexes and antioxidant indexes in different lactation stages of dairy cows, and a multiple linear regression model on the nutritional status indexes and antioxidant indexes was established. The experiments were conducted as a 2×6 (milk yield:high yield, ≥ 35 kg/d or low yield, <35 kg/d; lactation stage:prepartum, postpartum, early-lactation period, mid-lactation period, late-lactation period and dry period) double-factor completely randomized experiment design. A total of 240 Holstein cows with similar body weight[(550±10) kg], parity[(2.08±0.47) parities], body condition (3.0 to 3.5 points) were randomly divided into 12 groups with 20 cows per group. The results showed that the serum β-hydroxybutyric acid (β-HB), vitamin A (VA) contents and catalase (CAT) activity of high-yield dairy cows were significantly higher than those of low-yield dairy cows (P ≤ 0.05). The serum vitamin E (VE), zinc (Zn) contents and thioredoxin reductase (TrxR) activity in prepartum of dairy cows were lower, while the total superoxide dismutase (T-SOD), glutathion peroxidase (GSH-Px) and CAT activities were higher. The serum glucose (GLU), VA, VE, selenium (Se) contents and T-SOD, GSH-Px activities in postpartum were lower, while the non-esterified fatty acids (NEFA), β-HB, malondialdehyde (MDA) contents and CAT activity were higher. The serum GLU, VA, Se, copper (Cu) contents, total antioxidant capacity (T-AOC), and T-SOD, GSH-Px, CAT activities were lower in early-lactation period, while the MDA content was higher. The serum Se content was lower in mid-lactation period, while the Zn content was higher. The Se, Zn and MDA contents in late-lactation period were lower, while the GLU content and TrxR activity were higher. The NEFA and Zn contents in dry period were lower, while the GLU content and GSH-Px activity were higher. The lactation stage and milk yield had significantly interaction effects on the serum Se, Zn contents, T-AOC, GSH-Px and TrxR activities of dairy cows (P ≤ 0.05). The results of multiple regression analysis showed that serum antioxidant index such as MDA content had a significantly positive correlation with serum nutritional status indexes such as NEFA and β-HB contents (P ≤ 0.05), and had a significantly negative correlation with VA, VE, Se, Zn and Cu contents in the postpartum and early-lactation period (P ≤ 0.05). However, the multiple regression relationships between serum antioxidant indexes such as T-AOC, T-SOD and GSH-Px activities with the above nutritional status indexes showed the opposite results to MDA content. In summary, the serum nutritional status indexes and antioxidant indexes of dairy cows are significantly affected by the lactation stage, and there are significant multivariate regression relationships between the serum nutritional status indexes such as NEFA, β-HB, VA, VE, Se, Zn, Cu contents and the antioxidant indexes such as T-AOC, T-SOD and GSH-Px activities, and MDA content.