Bioactive lipids, such as platelet-activating factor, prostaglandins, and leukotrienes, convey febrigenic signals to the brain in response to bacterial infections, predominately as complexes with carrier proteins, such as α-1-acid-glycoprotein (AGP). Concentrations of acute phase proteins, like AGP, change by >25% in response to inflammation, and are part of the innate immune system. AGP binds and potentially enhances the activity of platelet-activating factor, the most proximal mediator of endotoxin-induced fevers. To determine the rectal temperature dose response of sheep to central AGP administration, nonlactating, non-pregnant, adult (≥1 yr of age) mixed breed black face ewes (n = 4) weighing 79.0 ± 5.0 (SD) kg were ovariectomized and surgically implanted with a cannula into a lateral ventricle of the brain. Ewes were kept indoors in individual pens with a 12-h light/dark photoperiod and approximately 22–24°C. Ewes were fed a diet calculated to meet 100% of daily maintenance requirements and had ad libitum water. Ewes received 1 of 4 treatments [0 (control), 12 (low), 60 (medium), or 300 (high) µg/kg BW AGP (AGP from bovine plasma; Sigma Aldrich Co., Saint Louis, MO)] administered in 500 µL of sterile, nonpyrogenic, isotonic, 0.9% sodium chloride into the lateral ventricle. Treatments were tested negative for lipopolysaccharide contamination by the limulus amebocyte lysate assay. Rectal temperature was determined at −72, −48, −24, −2, 0, 2, 4, 6, 8, 12, 24, 36, and 48 h relative to treatment. The study was repeated until all sheep received all treatments with a 10-d washout period between treatments. Data were analyzed using procedures for repeated measures with JMP software (version 10.0.0; SAS Inst. Inc., Cary, NC) and tested for effects of replication, treatment, time, and treatment × time interaction. There was no effect of treatment (P = 0.54) or replication (P = 0.86), but there was an effect of time (P < 0.0001) and treatment × time interaction (P = 0.002). Rectal temperatures were greater (P < 0.05) with high dose compared with control at 6, 8, and 12 h or low dose at 6 and 8 h. Thus, central AGP administration can increase rectal temperature in sheep.