N-(2,4-dichlorophenyl)-5-methyl-1,2-oxazole-3-carboxamide (UTL-5g) is a small-molecule chemoprotector against cisplatin and radioprotector against radiation. To further investigate its protective effects, we evaluated whether UTL-5g protects mice in a septic shock animal model. The two metabolites of UTL-5g, 5-methylisoxazole-3-carboxylic acid (Isox) and 2,4-dichloroaniline (DCA) were also evaluated side-by-side with UTL-5g. First, mice were pretreated with UTL-5g, Isox, and DCA before the i.p. injection of lipopolysaccharide (LPS)/D-(+)-galactosamine hydrochloride (D-Gal), respectively. Oral administration of both UTL-5g and Isox increased mouse survival while DCA did not, indicating that Isox is an active metabolite of UTL-5g while DCA is not. In the second study, mice were pretreated with UTL-5g or Isox individually by i.p. injection each at 30 mg/kg before LPS/D-Gal injection. The survival rates for both UTL-5g and Isox were better than those found for oral administration. In the third study, the same molar dose of UTL-5g and Isox by i.p. injection was used respectively and the results showed that UTL-5g had a better protective effect than Isox. In the fourth study, a protocol similar to the third study was used but blood samples were collected from the orbital plexus two hr after LPS/D-gal treatment. The results showed that UTL-5g lowered blood levels of both TNF- and TGF- elevated by LPS/D-gal. In summary, pretreatment of UTL-5g protected mice treated with LPS/D-Gal and the protection was related to the lowering of TNF- and TGF- levels elevated by LPS/D-Gal. In addition, UTL-5g appeared to be both an active drug and a prodrug wherein Isox is the active metabolite.