Although antioxidant therapy has been introduced into early post burn protocols to prevent oxidative injury, it is still not known how they effect the cellular immunity which was already depressed due to thermal injury. To investigate the effect of antioxidant therapy on postburn immunosuppression following burn injury in a rat model, well known antioxidants: allopurinol (50 mg/kg/day), desferrioxamine (15 mg/kg/day), PEG-catalase (PEG-CAT) (1200 U/kg/day), N-acetylcysteine (NAS) (1 mg/kg/day) and vitamin-C (Vit-C) (0.5 mg/kg/day) were given for 7 days following thermal injury. The immunologic status of the rat was studied using two in vivo measures at seventh day following (30% TBSA) full-thickness burn injury. The contact hypersensitivity response (CHR) of rats, and their ability to induce a host versus graft reaction (HVGR) in the popliteal node were used to assess immune system as in vivo measures. The use of mentioned antioxidants resulted in significant improvement (between P < 0.05 and P < 0.001) of burn induced immunosuppression as reflected by CHR. The treatment with allopurinol and PEG-CAT (P < 0.01) significantly improved, while desferrioxamine, NAS and Vit-C improved, but not significantly, HVG reaction in burned rats. This study demonstrated that a large burn was profoundly immunosuppressive and early intervention of antioxidant therapy was able to significantly restore cell-mediated immunity as reflected by two in vivo assays.