Oxidative stress may be important in early lactation cows due to high metabolic demands. Modifying dietary starch may alter glucose utilization, modify oxidative metabolism and, consequently, increase oxidative stress. To test this hypothesis, early lactation primiparous cows underwent a short-term dietary starch restriction followed by realimentation. At calving, 10 Friesian primiparous cows were randomly assigned to two groups and given a basal starch diet (BSD, 249 g/kg of starch dry matter (DM)) in the form of a total mixed ration until 42 days in milk (DIM). Afterwards, five cows (CTR) continued to receive the same diet and five cows (EXP) were allotted to experimental diets: low starch diet (LSD, 210 g/kg starch DM) from 43 to 65 DIM followed by high starch diet (HSD, 283 g/kg starch DM) from 66 to 85 DIM and BSD from 86 to 94 DIM. Blood samples were collected at 37, 50, 60, 70, 80, and 94 DIM to measure total plasma glutathione (GSH), thiobarbituric acid reactive substances (TBARS), and erythrocyte glutathione peroxidase (GPx) activity as indicators of oxidative stress, N-acetyl-ß-D glucosaminidase (NAGase), lysosyme, and white blood cell counts as indicators of immune response. Metabolic adaptations were evaluated by glucose, non-esterified fatty acids (NEFA), beta-hydroxy-butyrate (BOHB), insulin, and GH concentrations, and the acid/base balance. Milk yield was not significantly different between groups throughout the experiment and was correlated with TBARS (r 0·284; P 0·05) and GSH (r = 0·294; P 0·05). Estimated energy intake was significantly higher in the EXP group at 70 DIM only (P 0·05). Plasma glucose was significantly lower in the EXP group at 50, 60 (P 0·001) and 80 DIM (P 0·05), and was correlated with GSH (r = 0·348; P 0·01) and TBARS (r = 0·367; P 0·01). Plasma NEFA decreased overall in both groups (P 0·01). EXP was lower than CTR in concentrations of plasma BOHB at 70 DIM (P 0·05) and plasma insulin at 60 (P 0·001), 80 and 94 (P 0·05) DIM. Plasma TBARS, GSH and GPx increased throughout (P 0·01) in both groups. This was delayed in the EXP group following introduction of LSD; significant differences between groups at 60 (P 0·01), 80 and 95 (P 0·05) DIM for TBARS, and at 70 (P 0·01) and 80 (P 0·05) DIM for GPx. Indicators of immune response and plasma bicarbonates did not differ between groups. Blood pH was significantly lower in the EXP group at 80 and 94 DIM (P 0·001). Blood pCO2 was significantly lower at 80 and 94 DIM (P 0·05) in the CTR group. While recovering from the negative energy balance, cellular metabolism probably shifted towards oxidative phosphorylation, with a consequent oxidative stress increase. LSD delayed this recovery in the EXP group and thus reduced GSH synthesis. In conclusion, the diet starch content may alter the control of oxidative stress and expose animals to oxidative injuries.