Vitamin C (VC) is a vital micronutrient for humans and some other mammals and also has antioxidant activity. Stress-induced elevation of glucocorticoid production is well known to cause immunosuppression. This study evaluated the effect of high VC intake on glucocorticoid-induced immune changes in mice. Senescence marker protein 30 knockout (SMP30-KO) mice with genetic VC deficiency were fed a diet containing the recommended VC content (20 mg/kg/day; 0·2%VC group) or a high VC content (200 mg/kg/day; 0·2%VC group) for 2 months, then dexamethasone was given by intraperitoneal injection. After administration of dexamethasone, the plasma ascorbic acid concentration decreased significantly in the 0·02%VC group and was unchanged in wild-type C57BL/6 mice on a VC-deficient diet (wild-type group), while it was significantly higher in the 0·2%VC group than in the other two groups. In the 0·02%VC and wild-type groups, dexamethasone caused a significant decrease of cluster of differentiation (CD) 4+ and CD 8+ T cells among splenocytes, as well as a significant decrease of interleukin (IL)-2, IL-12p40, and interferon-gamma protein production by splenocytes and a significant decrease of T cell proliferation among splenocytes. In the 0·2%VC group, these dexamethasone-induced immunosuppressions were improved when compared with the other two groups. In addition, reduction of the intracellular levels of ascorbic acid, superoxide dismutase, and glutathione in splenocytes by dexamethasone, as well as elevation of thiobarbituric acid-reactive substances, were significantly suppressed in the 0·2%VC group. These findings suggest that high dietary VC intake reduces glucocorticoid-induced T cell dysfunction by maintaining intracellular antioxidant activity.