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A 2-part experiment was conducted to determine the effects of a blend of specialized mannan- and glucan-rich fractions of yeast (Select-TC, Alltech Inc.) on the health status and performance of steers during the first 2 mo of the feedlot period. Eighty crossbred steers were acquired from commercial sale barns in Mississippi and Georgia and transported to Purdue University. All animals were fed a corn silage-based receiving diet and were checked and treated daily for respiratory disease as needed following established treatment protocols. In Exp. 1, 64 steers (246.5 ± 4.7 kg initial weight) were blocked by BW and randomly allocated to 2 treatments to determine the impact of supplementation of a hydrolyzed mannan- and glucan-rich yeast fraction for 56 d on BW, ADG, daily DMI, and G:F: hydrolyzed yeast fed at 13 g (as-fed)/steer daily (TC) or nonsupplemented control (CON). Steers in Exp. 1 were housed in bedded pens with 2 animals per pen [n = 16 pens (32 steers)/treatment]. In Exp. 2, 16 steers (247.1 ± 5.4 kg initial BW) were similarly allotted to 2 treatments (CON and TC), individually penned, and subjected to a lipopolysaccharide (LPS) endotoxin challenge on day 62 or 63 after the start of the study to determine the animal's response to an inflammatory agent. Serum samples and rectal temperatures were taken every half an hour from -2 to 8 h relative to LPS injection from steers in Exp. 2. Data were analyzed as a complete randomized block design using the MIXED procedure of SAS. Morbidity for both experiments did not differ (P ≥ 0.16). Weight, ADG, DMI, and G:F did not differ among treatments (P ≥ 0.32) in Exp. 1. After the LPS infusion in Exp. 2, rectal temperatures (P = 0.03) and serum NEFA concentration (P = 0.04) were decreased in TC compared with CON steers. Concentrations of blood urea nitrogen (P = 0.31), glucose (P = 0.70), insulin (P = 0.57), and cortisol (P = 0.77) did not differ by treatment after LPS administration. Serum IL-6 concentrations were decreased (P < 0.0001), and interferon-γ concentrations tended to be greater (P = 0.07) in TC compared with CON steers after LPS infusion. Serum cytokine and metabolite results indicate that Select-TC improved health and metabolic status of LPS-challenged cattle, but this did not result in quantifiable improvements in performance in the conditions observed in this study., (© The Author(s) 2018. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)