Chlorpyrifos (CPF), an organophosphorus insecticide is known to cause ill health in non-target animals by inducing oxidative stress. In this study influence of cold stress (15°C and 20°C) and age as modulating factors on CPF induced oxidative stress was addressed to assess age-related differences and vulnerability in central nervous system of rats. The results indicated an interaction with age and cold exposure resulting in marked decreased activity levels of SOD (P < 0.05), CAT (P < 0.05), GPx (P < 0.05), GST (P < 0.05) followed by increased MDA (P < 0.05) and decreased GSH levels (P < 0.05). The ANOVA and Post-hoc analysis showed that antioxidant enzymes decreased significantly (P < 0.05) on CPF exposure. Moreover synergistic action of CPF and cold stress at 15°C caused higher inhibition on comparison with CPF and cold stress alone and together at 20°C indicating the extent of peroxidative damage in discrete regions of CNS. Further this study showed young individuals to be more sensitive than adults.