Neonates are particularly susceptible to malnutrition due to their limited reserves of micronutrients and their rapid growth. In the present study, we examined the effect of vitamin C deficiency on markers of oxidative stress in plasma, liver and brain of weanling guinea pigs. Vitamin C deficiency caused rapid and significant depletion of ascorbate (P,0001), tocopherols (P,0001) and glutathione (P,0001), and a decrease in superoxide dismutase activity (P¼0005) in the liver, while protein oxidation was significantly increased (P¼0011). No changes in lipid oxidation or oxidatively damaged DNA were observed in this tissue. In the brain, the pattern was markedly different. Of the measured antioxidants, only ascorbate was significantly depleted (P,0001), but in contrast to the liver, ascorbate oxidation (P¼0034), lipid oxidation (P,0001), DNA oxidation (P¼013) and DNA incision repair (P¼0014) were all increased, while protein oxidation decreased (P¼0003). The results show that the selective preservation of brain ascorbate and induction of DNA repair in vitamin C-deficient weanling guinea pigs is not sufficient to prevent oxidative damage. Vitamin C deficiency may therefore be particularly adverse during the neonatal period.