Abstract: Heavens, KR, Szivak, TK, Hooper, DR, Dunn-Lewis, C, Comstock, BA, Flanagan, SD, Looney, DP, Kupchak, BR, Maresh, CM, Volek, JS, and Kraemer, WJ. The effects of high intensity short rest resistance exercise on muscle damage markers in men and women. J Strength Cond Res 28(4): 1041–1049, 2014—Within and between sexes, universal load prescription (as assigned in extreme conditioning programs) creates extreme ranges in individual training intensities. Exercise intensity has been proposed to be the main factor determining the degree of muscle damage. Thus, the purpose of this study was to examine markers of muscle damage in resistance-trained men (n = 9) and women (n = 9) from a high intensity (HI) short rest (SR) (HI/SR) resistance exercise protocol. The HI/SR consisted of a descending pyramid scheme starting at 10 repetitions, decreasing 1 repetition per set for the back squat, bench press, and deadlift, as fast as possible. Blood was drawn pre-exercise (pre), immediately postexercise (IP), 15 minutes postexercise (+15), 60 minutes postexercise (+60), and 24 hours postexercise (+24). Women demonstrated significant increases in interleukin 6 (IL-6; IP), creatine kinase (CK; +24), myoglobin (IP, +15, +60), and a greater relative increase when compared with men (+15, +60). Men demonstrated significant increases in myoglobin (IP, +15, +60, +24), IL-6 (IP, +15), CK (IP, +60, +24), and testosterone (IP, +15). There were significant sex interactions observed in CK (IP, +60, +24) and testosterone (IP, +15, +60, +24). Women completed the protocol faster (women: 34:04 ± 9:40 minutes, men: 39:22 ± 14:43 minutes), and at a slightly higher intensity (women: 70.1 ± 3.5%, men 68.8 ± 3.1%); however, men performed significantly more work (men: 14384.6 ± 1854.5 kg, women: 8774.7 ± 1612.7 kg). Overall, women demonstrated a faster inflammatory response with increased acute damage, whereas men demonstrated a greater prolonged damage response. Therefore, strength and conditioning professionals need to be aware of the level of stress imposed on individuals when creating such volitional high intensity metabolic type workouts and allow for adequate progression and recovery from such workouts.