Organophosphate compounds are the most widely employed insecticides in countries with high agriculture activity. On average, organophosphates cause 3 million people to poison and 200 000 deaths per year due to food chain or occupational, accidental, or suicidal exposure. Our study aimed to research selenium’s protective role against the toxic action of CPF, one of the most commonly used organophosphates, with an experimental model formed with rats. A total of 56 male SD rats were distributed into seven groups as follows: control (tap water), sham (corn oil), group I (5.4 mg/kg CPF), group II (13.5 mg/kg CPF), group III (3 mg/kg Se), group IV (5.4 mg/kg CPF+Se), and group V (13.5 mg/kg CPF+Se). Following 6 weeks of oral exposure, there were significant changes in AChE activity, biochemical and hematological parameters, and trace element levels in CPF-treated rats. In the high-dose CPF group, RBC values, Hb, and Hct decreased, and values of WBC, AST, ALT, ALP increased (p < 0.001) significantly compared to control, sham, and Se groups. While there was no significant change in zinc level, the copper and selenium levels were significantly higher in group IV than in control (p < 0.001) and sham (p < 0.05, p < 0.01, respectively) groups. Moreover, max. O.R.L. was found statistically more elevated in the high-dose CPF group compared to control, sham, and Se groups (p < 0.05, p < 0.05, and p < 0.01, respectively). All results indicated that Se is an antioxidant that reduces the toxic effects caused by CPF. Employing combinations of chlorpyrifos and selenium appeared greatly in restoring the harmful effects of CPF exposure.