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PURPOSE: To examine the influence of the Ultraman triathlon (3 days of non-continuous racing; stage 1: 10 km swim and 144.8 km cycle; stage 2: 275.4 km cycle; stage 3: 84.4 km run) on circulating plasma concentrations of whole-body (CRP, IL-6, and IL-10) and gut-specific inflammatory markers (IL-17 and IL-23) in trained participants, and determine whether these variables influence performance. METHODS: Fourteen triathletes (age: 39 ± 8 yrs; 12 men, 2 women) were evaluated pre-race and post-race for circulating concentrations of CRP, IL-6, IL-10, IL-17, and IL-23. Blood samples were drawn two days prior to stage 1 (1600 h) and one day after stage 3 (1200 h). Plasma biomarker concentrations were determined by ELISA according to manufacturer’s instructions. Data were analyzed with SPSS and significance was accepted at p < 0.05. Values are reported as means ± SD. RESULTS: Plasma CRP significantly increased from pre-race (266.27 ± 276.18 ng/mL) to post-race (25,891.94 ± 12,888.65 ng/mL; p < 0.001). Plasma IL-10 increased from pre-race (3.46 ± 2.98 pg/mL) to post-race (5.15 ± 1.89 pg/mL). Pre-race concentrations of IL-6 were below detectable limits; post-race IL-6 concentrations were 4.00 ± 3.74 pg/mL. Both pre-race and post-race concentrations of IL-17 and IL-23 were below detectable limits. Pearson’s correlation between mean finish time and post-race CRP and post-race IL-10 was 0.35 and 0.54 (p < 0.05), respectively. CONCLUSIONS: The significant increase in CRP during the race may have been due to muscle damage. The greater anti-inflammatory capacity of the athletes likely led to increased clearance of IL-6, IL-17, and IL-23 the day after the race; the increase in IL-10 concentrations during the race reflect this anti-inflammatory response. A significant positive correlation between post-race IL-10 concentrations and mean finish time may indicate that a relationship between anti-inflammatory responses and performance exists.