Activated immune cells are obligate glucose utilizers and a large lipopolysaccharide (LPS) IV dose causes severe hypoglycemia. Therefore, study objectives were to use the quantity of glucose needed to maintain euglycemia during an IV bolus endotoxin challenge as a proxy for the immune system’s glucose requirement. Fasting growing Holstein steers (148 ± 9 kg) were jugular catheterized bilaterally and assigned to 1 of 3 treatments: control (CON; 3 mL sterile saline; n = 5), LPS-infused (LPS; E. coli 055:B5; 1.5 μg/kg BW; n = 5), and LPS + euglycemic clamp (LPS-Eu; 1.5 μg/kg BW; 50% dextrose infusion to maintain euglycemia; n = 5). Following infusion, blood glucose was determined every 10 min and dextrose infusion rates were adjusted in LPS-Eu calves to maintain euglycemia for 12 h. Plasma samples were obtained 3, 6, 9, and 12 h relative to bolus infusion for further analysis. All calves survived the LPS challenge. Rectal temperature was increased in LPS (0.6°C, P = 0.03) and tended to be increased in LPS-Eu (0.5°C, P = 0.06) relative to CON calves. LPS and LPS-Eu calves were hyperglycemic for 3 h post-bolus, likely due to hepatic glycogenolysis. Thereafter, blood glucose was markedly decreased in LPS relative to both CON and LPS-Eu calves (30%, P < 0.01). Blood lymphocytes, and platelets were increased in LPS and LPS-Eu calves relative to CON (53 and 56%, respectively; P < 0.01). Ionized calcium was decreased in both LPS and LPS-Eu calves relative to CON (18%, P < 0.01). White blood cells decreased or tended to decrease in LPS-Eu and LPS (59%, P = 0.03; 44%, P = 0.06; respectively) relative to CON. During the 12 h, 516 ± 65 g of infused glucose was required to maintain euglycemia. If the amount of glucose required to maintain euglycemia can be used as a proxy, then the glucose requirements of an activated immune system are approximately 43 g/h in growing ruminants.