Background/Objective: This study evaluated the influence of sex on changes in cytokines, heat shock proteins (HSPs), and oxidative stress in response to a single bout of total body resistance exercise. Methods: Sixteen healthy volunteers (8 men and 8 women), active and recreationally trained in resistance exercise, were subjected to a single bout of total body resistance exercise (3 × 8–10 repetition maximum, 10 exercises, rests periods of 90–120 seconds). Serum creatine kinase (CK), interleukin (IL)-6, IL-10, tumor necrosis factor-α, HSP60, HSP70, thiobarbituric acid reactive substance, and reduced glutathione were assessed at pre-protocol, and 1 hour, 4 hours, and 24 hours post-protocol. Results: Both men and women had a similar increase in CK (p < 0.05) activity at 24 hours post-exercise. Significant sex differences were observed for IL-6. In the men, an increase from baseline was noted at 1 hour for IL-6. In women, an increase from baseline was noted at 4 hours only for IL-6. There was a significant correlation between peak IL-6 blood level and CK level at 24 hours only in the women. No significant changes were observed in IL-10, tumor necrosis factor-α, HSP60, HSP70, thiobarbituric acid reactive substance, and reduced glutathione. Conclusion: Acute total body resistance exercise altered circulating levels of IL-6 and sex differences existed in the temporal pattern and magnitude of this response.