Objective: To evaluate the protective value of quercetin, gossypin, Hippophae rhamnoides (HR) flavone and tocopherol acetate against the systemic toxicity of percutaneously administered sulphur mustard (SM) in mice. Materials and Methods: Quercetin, gossypin, HR flavone or tocopherol acetate (200 mg/kg, i.p.) were administered just before percutaneous administration of SM and protection against the SM lethality was evaluated. In another experiment quercetin, gossypin, HR flavone or tocopherol acetate were administered against 2 LD50 SM. The animals were sacrificed seven days post SM administration and various biochemical parameters were estimated. Results: The protection against the lethality of SM was very good with the flavonoids (quercetin = 4.7 folds; gossypin = 6.7 folds and HR flavone = 5.6 folds), compared to no protection with tocopherol acetate (0.7 fold). SM (2 LD 50 ) showed decrease in reduced and oxidised glutathione (GSH and GSSG) levels, and an increase in malondialdehyde level (MDA). Oxidative stress enzymes like glutathione peroxidase, glutathione reductase and superoxide dismutase were significantly decreased. The total antioxidant status was also significantly decreased. Additionally, there was a significant increase in red blood corpuscles and hemoglobin content. All the flavonoids significantly protected the GSH, GSSG and MDA, and also the hematological variables. Tocopherol acetate failed to offer any protection in those parameters. Gossypin protected glutathione peroxidase, while HR flavone protected both glutathione reductase and glutathione peroxidase significantly. The decrease in body weight induced by SM and the histological lesions in liver and spleen were also significantly protected by the flavonoids but not by tocopherol acetate. Conclusion: The present study supports that SM induces oxidative stress and flavonoids are promising cytoprotectants against this toxic effect.