We have conducted studies with juvenile yellow perch (Perca flavescens) over a period of 20 weeks to address the question of the interaction between water- and lipid-soluble antioxidant vitamins. Fish (2·25±0·14 g) were divided into twelve groups, and triplicate groups were fed one of four casein-based, semi-purified diets formulated to contain low or high vitamin E levels of either 5 or 160 mg/kg without or with vitamin C supplementation (250 mg/kg). Diets were designated as −C−E, −C+E, +C−E, or +C+E, respectively. The fish fed the +C+E diet showed significantly higher weight gain, feed intake, and feed efficiency than the groups fed vitamin C-deficient diets. Total ascorbate concentrations of liver were significantly higher in fish fed vitamin C-supplemented diets than in fish fed the vitamin C-deficient diet after 16 and 20 weeks. The liver α-tocopherol concentrations were increased by supplemental vitamin C in vitamin E-deficient dietary groups which indicates a sparing or regenerating effect of vitamin C on vitamin E. Fish fed vitamin C-deficient diets (−C−E and −C+E) exhibited severe deficiency symptoms, such as scoliosis, lens cataracts, anorexia, and haemorrhages. The cumulative mortality was significantly higher in the −C−E groups. The thiobarbituric acid-reactive substances value was significantly higher in blood plasma of fish fed a diet unsupplemented with both vitamins. The findings in the present study with yellow perch support the hypothesis that vitamin C regenerates and/or spares vitamin E in vivo.