Endotoxemia associated with Gram-negative sepsis is an emergency clinical state that causes rapid biochemical changes and substantial mortalities in livestock. The present study aimed to investigate the therapeutic effect of vitamin C on blood gases, acid-base balance and nitric oxide in lamb model of lipopolysaccharide [LPS]- induced endotoxemia. The study was conducted on 15 lambs, 3-5 months of age. Animals were randomly grouped into 3 groups, five each as followings: Group 1 (control): received only normal saline, Group 2: received only LPS at dose 25 µg/kg B.W. and Group 3: received vitamin C at dose 20 mg/kg B.W. one hour before LPS infusion. Saline (10 ml) or LPS in saline were infused through jugular canula. The experimental fever elicited by iv injection of LPS 25 μg/kg/ B.W. was accompanied by metabolic acidosis, hypoxemia and significance increased production of nitric oxide. A significant decrease in blood pH, base excess and HCO₃⁻ was noticed during fever. Although the concentrations of HCO₃⁻ were decreasing till the end of the experiment, there was no substantial falls in PCO₂ for compensation of the noticed acidosis. However, hypoxemia was evident as indicated with marked reduction in oxygen saturation and oxygen tension. Nitric oxide level increased during the period of experiment and reached peak 5 hours post LPS administration. Pretreatment with i.v. 20 mg/kg B.W. of vitamin C an hour pre LPS administration reduced the febrile response and reversed the postpyrogen changes in pH, HCO₃⁻ and nitric oxide. Possible mechanisms by which vitamin C could affect the LPS-induced disturbances of acid-base balance are being considered. Finally, it could be concluded that vitamin C pretreatment prevented LPS –induced metabolic acidosis and nitric oxide production.