Eighteen grade Angora goats (BW 14 kg) and 18 Barbados Blackbelly × Dorset sheep (BW 24 kg), all wethers, were fed coastal bermudagrass hay (84% neutral detergent fiber, 6% crude protein) supplemented with alfalfa hay or cotton seed meal during an 84-day feeding trial. On day 28, daily treatment with slaframine (SF; 30 μg kg-1 BW), a parasympathomimetic with high affinity for the gastrointestinal tract, or physiological saline was initiated. On day 70, blood samples were obtained at hourly intervals for analyses of glucose (GLU), nonesterified fatty acids (NEFA), urea nitrogen (PUN), insulin (INS), glucagon (GLN), thyroxine (T4), and triiodothyronine uptake (T3U). Plasma concentrations of GLU, NEFA and PUN did not differ between species. Goats had higher (P < 0.05) concentrations of INS, T3, and lower percentage T3U than sheep. The INS to GLN ratio (I/G), was also greater (P < 0.05) in goats. SF increased (P < 0.05) GLU and NEFA and decreased (P < 0.01) PUN. INS tended to decrease and GLN to increase in response to SF, resulting in a lower (P < 0.05) I/G. SF increased (P < 0.05) T4 concentrations and lowered (P < 0.05) the percentage T3U. Protein supplementation increased (P < 0.01) PUN concentrations without affecting plasma concentrations of GLU and NEFA. Plasma concentrations of INS and GLN did not change in response to protein supplementation, while metabolite and hormonal changes were minimal, but SF administration resulted in major changes in blood metabolite and hormone profiles.