This study investigated the effects of combined supplementation with vitamin E and C against oxidative stress (OS) caused by intermittent cold exposure (ICE) in the hypothalamus (HY) of aging male Wistar rats [adult (3-months), middle-aged (18-months) and old (24-months)]. Each age was divided into sub-groups: control (CON), cold-exposed at 10 C (C10), cold-exposed at 5 C (C5), supplemented control (CON+S) and supplemented cold-exposed at either 5 C (C5+S) or 10 C (C10+S). The supplement was a daily dose of 400 mg vitamin C and 50 IU of vitamin E/kg body weight. Cold exposure lasted 2 h/day for 4 weeks. All age groups exposed to cold showed increase in body mass and feeding efficiency. Feeding efficiency in the supplemented old group showed a statistically significant increase in the cold (p < 0.001). Age-related increases in levels of hydrogen peroxide (H2O2), protein carbonyl (PrC), advanced oxidation protein products and thiobarbituric acid reactive substances (TBARS) were further increased by cold in the HY. Cold reduced thiol(P-SH) levels and increased superoxide dismutase (SOD) and, catalase (CAT) activities as well as Hsp72 levels. However, supplementation lowered H2O 2, PrC and TBARS with decreases in Hsp72 levels and in SOD and CAT activities. These changes were concomitant with elevations in P-SH, vitamin E and C levels. The results show that the OS caused by ICE in the HY and its subsequent protection following supplementation is related to the intensity of ICE as well as age of the animal. Immunohistochemical studies are underway to examine the findings on ICE-induced oxidative injury in the HY, and the prospects for vitamin E and C supplementation in the senescent. © 2013 Springer Science+Business Media New York.