The study evaluated the effect of combination of chlorpyrifos (CPF) and deltamethrin (DLT) on serum lipid profiles and oxidative stress in rats, and the mitigating role of alpha-lipoic acid (ALA). Thirty male rats were used for the 120-day study. Serum samples obtained at termination were evaluated for the levels of triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), malondialdehyde (MDA), and the activities of antioxidant enzymes. The levels of low-density lipoprotein-cholesterol (LDL), very low-density lipoprotein-cholesterol (VLDL), and atherogenic index (AI) were calculated. The pesticide combination elevated the levels of TG, TC, LDL, VLDL, AI, and MDA, and decreased HDL level, and activities of CAT, SOD, and GPx. The alterations induced by CPF and DLT were alleviated by ALA, partly through its antioxidant properties. In conclusion, co-exposure to DLT and CPF altered serum lipids and increased oxidative stress changes in the rats, which were ameliorated by ALA.