Simple Summary High summer temperatures in desert regions decrease weight gain, feed efficiency, carcass weight, and meat tenderness in feedlot sheep, which is associated with insufficient availability of dietary energy by increasing energy requirements for thermoregulation. So, hair male and female lambs were fed thiamine diphosphate to evaluate its effect as glucogenic cofactor on physiological variables, feedlot growth, carcass traits and meat quality under hot desert conditions. Thiamine improved heat loss along the body surface, without changing rectal temperature and respiratory rate. Furthermore, it reduced feed intake in females but not in males. Regardless of gender, thiamine did not modify growth rate, carcass yield, fat deposition, and color and hardness in meat. Therefore, this heat stress mitigation strategy effectively increased dietary energy efficiency in ewe lambs but was ineffective for male lambs.Abstract Twenty Dorper x Katahdin lambs (10 males and 10 females) were distributed in a 2 x 2 factorial arrangement under a randomized complete block design to evaluate the effects of thiamine diphosphate (TD) supplementation (0 vs. 250 mg/kg feed) and gender (males vs. females) on physiological responses, feedlot performance, carcass characteristics, and meat quality in a hot desert environment. The average temperature and temperature-humidity index recorded during the study were 33.60 degrees C and 35.89 units, respectively, indicating an extremely severe heat stress environment for lambs. Study variables were not affected (p >= 0.12) by the TD x gender interaction, except for dry matter intake (DMI; p = 0.02) and some head temperatures (p <= 0.05) and carcass zoometric measurements (p <= 0.05). In females, but not in males, TD decreased DMI and increased thorax depth, as well as eye, ear, and forehead temperatures. Overall, TD increased (p <= 0.05) surface temperatures of neck, shoulder, loin, rump, forelimb, testicles, vulva, anus, and perineum without affecting (p >= 0.58) rectal temperature and respiratory rate. Supplemental TD did not affect (p >= 0.16) growth rate, feed efficiency, carcass weight and yield, Longissimus thoracic muscle area, backfat thickness, internal fat deposition, wholesale cut yields, and meat quality traits. In conclusion, in hair ewe lambs but not in male lambs, TD supplementation at a dose of 250 mg/kg of feed in the fattening diet is an HS mitigation strategy that improves dietary energy efficiency for growth and carcass mass deposition. Furthermore, thiamine increases heat losses through the body surface, regardless of gender.