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Sulfur mustard (SM; 2,2’-dichloro diethyl sulfide) is an alkylating chemical warfare agent and inflicts serious blisters upon contact with human skin. Monofunctional sulfur mustard, 2-chloroethyl ethyl sulfide (CEES) has been used as a simulant for detection, mechanism of action and protection studies of SM. The objective of this study is to compare the toxicity of SM and CEES using oxidative stress markers with reference to the route specific toxicity, through percutaneous (p.c.), subcutaneous (s.c.), oral (p.o.) and intraperitoneal (i.p.) routes in mice. The LD50 of SM was determined to be 9.7, 13.5, 19.3 and 4.8 mg/kg through p.c., s.c., p.o. and i.p. routes, respectively. Notably, SM through i.p. route was found to be the most toxic, the p.c. route was more toxic than s.c. and p.o. routes. The LD50 of CEES was determined to be 1425, 100, 566 and 17.7 mg/kg through p.c., s.c., p.o. and i.p. routes, respectively. In the case of CEES the s.c. route was more toxic than p.c. route, which is more typical of toxic chemicals. At 1 and 2 LD50, death after CEES administration was within 1 to 2 days, while death following SM administration was much delayed (> 6 days). Equitoxic doses (0.5 LD50) of SM and CEES were administered through all the routes: and it was observed that the p.c. route showed a significant decrease in body weight in SM. Depletions in reduced and oxidized glutathione, compared to CEES, were also observed 7 days after administration. However, increases in malondialdehyde and reactive oxygen species levels were observed in both SM and CEES through all routes, 7 days after administration. DNA fragmentation was observed in SM through the i.p. route and in CEES through the p.o., i.p. and s.c. routes (also at 0.5 LD50 dose)