The aim of this article is to review current literature on the response of soluble interleukin-6 receptor to exercise and identify a potential role for sIL-6R in skeletal muscle function. We also provide novel data on the impact of eccentric exercise on circulating levels. The aim of the research study was to investigate changes in plasma concentration of soluble interleukin-6 receptor (sIL-6R) and soluble glycoprotein 130 (sgp130) during recovery from exercise-induced muscle damage (EIMD) up to 72 h and their relationship with delayed onset muscle soreness (DOMS) and muscle function. 18 participants attended the laboratory on 4 consecutive days. On the first day, participants completed 6 sets of 10 repetitions of unilateral eccentric-concentric knee flexions at a test speed of 1.05 rad.s(-1) using a Cybex Isokentic dynamometer to induce muscle damage of the hamstrings. Prior to the eccentric exercise bout and each subsequent morning, following an overnight fast, participants had a venous blood sample taken which was centrifuged immediately and plasma frozen at -80 degrees C until later analysis. Plasma IL-6 and sgp130 were unchanged at any time point during recovery but sIL-6R was significantly reduced at 48 h and 72 h post-exercise (p < 0.05). Plasma sIL-6R was correlated with DOMS at 48 h post EIMD (r = 0.45, p < 0.05) and peak muscle torque at 24 h and 48 h following EIMD (r = -.42; p < 0.05; r = -.57; p < 0.01 respectively). Our novel finding that sIL-6R concentrations are decreased 2-3 days following a single bout of EIMD may reflect a regulatory mechanism controlling the influx of different leukocyte subpopulations into damaged tissue, although this needs to be confirmed by future studies. Our data suggests an association between sIL-6R, perception of pain and reduced peak muscle performance post-EIMD but further investigation is warranted to explore this relationship and implications for exercise performance.