The endurance sled dog is the ultimate endurance athlete in which to examine the exercise-associated acute phase and myokine responses that might be related to changes in muscle metabolism and damage. An inciting cause for increased C-reactive protein has yet to be elucidated, which might involve interleukin-6 and other myokines. To examine concentrations of interleukin-6 (IL-6), interleukin-15 (IL-15), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α), and markers of the inflammatory response of exercise; monocyte chemoattractant protein-1(MCP-1) and C-reactive protein (CRP) before, during, and after an endurance racing event. 26 sled dogs completing a 1650-km race. In a prospective study, cephalic venipuncture was performed before racing, at the midpoint, and after racing. Body weight and serum CRP, MCP-1, IL-15, IL-8, IL-6, and TNF-α concentrations were evaluated using enzyme-linked immunoabsorbance-based assays or a luminex multiplex assay. There were no significant differences in concentrations of IL-6, IL-15, IL-8, or TNF-α at the 3 time points, whereas there were significant increases in MCP-1 (median and range-start: 86pg/mL [30-1845]; midpoint: 179pg/mL [53-730]; finish: 180pg/mL [21-1294]; P<.01) and CRP (median and range-start: 18μg/mL [11-58]; midpoint: 76μg/mL [12-198]; finish: 60μg/mL [12-170]; P<.01) at the midpoint and race finish. There was a significant linear relationship between MCP-1 and IL-6 (R=0.68; P<.01). The inflammatory response to exercise increases as measured by MCP-1 during and after endurance exercise in sled dogs. IL-6 appears to be associated with MCP-1; however, the reasons for increases in the acute phase response (CRP) cannot be attributed to IL-6 or other myokines. IL-6 and MCP-1 concentrations might be useful in future investigations of exertional rhabdomyolysis.