This cross-sectional study examined the associations between serum interleukin-6 (IL-6) and muscle, bone, and fat parameters in recreationally active women. One-hundred forty-five women (48.7 ± 17.8 years; 164.4 ± 7.1 cm; 66.8 ± 10.7 kg; and 24.7 ± 3.9 kg/m2) underwent dual energy x-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) assessments to determine total and regional muscle, bone, and fat parameters. Muscle performance of the knee extensors was examined via isometric, isotonic, and isokinetic dynamometry assessments, and serum IL-6 was measured via enzyme linked immunosorbent assay. Serum IL-6 was inversely associated with thigh muscle cross-sectional area (mCSA, r = -0.28, p < 0.01); isometric strength (r = -0.19, p < 0.05); hip areal bone mineral density [aBMD] (r = -0.18, p < 0.05); trochanter aBMD (r = -0.23, p < 0.01); total body aBMD (r = -0.20, p < 0.05); cortical volumetric bone density at 38 and 66% tibia (r = -0.18 and r = -0.19, respectively, both p < 0.05), and 66% cortical thickness (r = -0.17, p < 0.05). These associations were present after adjusting for age, BMI, and physical activity. Thigh mCSA was significantly lower in the tertile possessing the greatest IL-6 compared to the lowest tertile (p < 0.01); after adjusting for age, body mass index, and physical activity. Collectively, these observations indicate that IL-6 is inversely associated with skeletal muscle and bone parameters independent of relevant confounders. These observations bolster the prognostic value of serum IL-6.