ABSTRACT Background: India is a land of agriculture, where the economy is based on cash crop cultivation. The wide and chronic use of pesticides for agriculture, domestic, and industrial purposes without protective measures has led to subsequent adverse health effects and further evaluation. It has become a major concern of public health due to its usage throughout the year among pesticide industrial workers, distributors and retail shopkeepers, agricultural field workers, and sprayers. Among the different types of pesticides (organochlorines, organophosphorus, carbamates, and pyrethroid compounds) used, quinalphos is the most common organophosphorus compound used in South India. These compounds were known to produce oxidative damage in the liver, kidney, bone marrow, brain, and intestine. Nonenzymatic antioxidants like vitamin C and E were found to alleviate the oxidative damage imposed by these pesticides. Thus, the present study aims to evaluate the effect of oral supplementation of vitamin E and vitamin C in comparison to exposure-free days on complete blood count, antioxidant enzymes, liver enzymes, and histopathological changes in the liver following exposure of male Wistar rats to quinalphos. Materials and Methods: This experimental study was done at XXXX after getting scientific and ethical committee clearance. A total of 24 adult male Wistar rats were divided randomly into four groups, with six in each group. Group A consists of animals not exposed to quinalphos for 60 days (control group), group B exposed to quinalphos for 60 days, group C exposed to quinalphos orally only for the first 30 days with exposure-free days for the next 30 days, and group D exposed to quinalphos orally for 60 days along with vitamin E and vitamin C oral supplementation. During exposure, quinalphos was administered at the dose of 3 mg/kg/day mixed with drinking water through oral gavage. Animals were sacrificed at the end of 60 days. Blood was collected by direct cardiac puncture, and the liver tissue was used for histopathological investigation. Data were analyzed with one-way ANOVA and post hoc Turkey’s test for intergroup comparison using SPSS 21.0 software. Results: RBC count (P = 0.011), Hb % (P = 0.000), and hematocrit (P = 0.000) were significantly reduced, whereas WBC count (P = 0.005) and neutrophil % (P = 0.001) significantly increased in the quinalphos-exposed group (group B) compared to other three groups. Liver enzymes, SGPT (P = 0.028) and SGOT (P = 0.343), were elevated, and the antioxidants catalase (P = 0.000) and glutathione peroxidase (P = 0.000) were significantly reduced in the quinalphos-exposed group when compared to the control and exposure free group. Histopathology of the liver showed diffuse necrosis of the hepatocytes with central venous congestion in quinalphos-exposed (group B) compared to the other three groups. The exposure-free group (group C) has shown better histopathological changes when compared to quinalphos exposure with (group D) and without (group B) vitamin C and E supplementation group. Conclusion: Quinalphos exposure orally results in anemia, leucocytosis with neutrophilia, liver damage, and oxidative stress. As evidenced by liver histopathology and altered antioxidant enzymes in the supplementation group compared to the group with exposure-free days, the toxic effects of quinalphos were less during exposure-free days. Thus, people occupationally exposed to quinalphos can alleviate the ill effects by having exposure-free days as interval breaks to remove the toxic accumulation of organophosphorus compounds.