This investigation determined whether inflammatory mediators 1) have diurnal variations, 2) respond to high-force eccentric exercise, and 3) associate with markers of muscle damage after high-force eccentric exercise. College-aged men and women (n=51) completed exercise (3x15 maximal eccentric elbow flexor actions using one arm) and control conditions in random order. Blood was collected pre-, 4, 8, 12, 24, 48, and 96 h post-exercise. Additional measures included maximal isometric force, and mid-biceps arm circumference (to detect swelling). Serum and plasma were analyzed for soluble tumor necrosis factor receptor-1 (sTNFR1), IL-6, C-reactive protein (CRP), cortisol, and creatine kinase (CK) activity. Relative to the 7:00 a.m. point in the control condition, diurnal decreases were measured at 12:00 and 4:00 p.m. for IL-6 and at 12:00, 4:00, and 8:00 p.m. for sTNFR1 and cortisol. sTNFR1, IL-6, CK, swelling, and soreness were higher in the exercise compared to the control condition. The largest of the inflammatory mediator responses was measured for IL-6 8 h post-exercise in the exercise (3.00 ± 3.59 pg·ml^-1) relative to the control condition (1.15 ± 0.99 pg·ml^-1). The IL-6 response (time-matched exercise -control concentration) at 8 h associated (r>0.282) with muscle soreness at 24 and 96 h, and the cortisol response at 8 h associated (r>0.285) with swelling at 8, 24, and 96 h. Thus, soreness and swelling, but not CK and strength loss, had a low association with the inflammatory response following eccentric exercise.