The present study aimed to evaluate the effect of chronic co-exposure to chlorpyrifos (CPF) and deltamethrin (DLT) on erythrocyte osmotic fragility, lipid peroxidation and the ameliorative effect of alpha-lipoic acid (ALA) on erythrocyte fragility. Thirty-six male Wistar rats divided into six groups of six rats each were used for the study. Groups I (S/oil) and II (ALA) were given soya oil (2 ml/kg) and ALA (60 mg/kg), respectively. Rats in group III (DLT) and IV (CPF) were exposed to DLT (6.25 mg/kg) and CPF (4.75 mg/kg) (1/20th of the previously determined LD50 of 125 mg/kg and 95 mg/kg, respectively, over a period of 48 h). Rats in group V (CPF + DLT) were co-exposed to CPF (4.75 mg/kg) and DLT (6.25 mg/kg), while those in group VI (ALA + CPF + DLT) were pretreated with ALA (60 mg/kg) and then co-exposed to CPF and DLT, 45 min later. The treatments were administered by gavage once daily for a period of 16 weeks. Blood collected at the end of the experimental period were analyzed for erythrocyte osmotic fragility and malondialdehyde (MDA) concentration. The study showed that chronic co-exposure to CPF and DLT resulted in an increase in erythrocyte fragility and MDA concentration which were ameliorated by supplementation with alpha-lipoic acid. The study concluded that repeated co-exposure to CPF and DLT elevated erythrocyte fragility probably due to increased lipid peroxidation, and pretreatment with alpha-lipoic acid ameliorated these alterations.