Introduction: The role of skeletal muscle health on preventing and ameliorating chronic disease is emerging. The improvements in skeletal muscle metabolism are likely mediated by myokines, such as myostatin, IL-6, and decorin. Whether or not basal skeletal muscle health contributes to the myokine response to Whole body vibration (WBV), an exercise mimetic, has yet to be elucidated. Methods: Data from Sixty-three young adults (32.5± 0.7 years, 57.1% female, 42.9% non-Hispanic Black) were included from a longitudinal twin cohort study. Skeletal muscle oxidative capacity (SMOC) was determined using near-infrared spectroscopy by measuring the rate of skeletal muscle oxygen consumption after stimulation and was represented as a rate constant averaged over three trials (AvgRC). The acute WBV protocol consisted of 10 cycles of 1 min of vibration exercise followed by 30s of standing rest. Blood was collected at baseline (PRE), immediately post, and 1h, 3h, and 24h post WBV and myokine concentrations of IL-6, myostatin, and decorin were measured at each of these timepoints. Participants were divided into two groups by SMOC: low skeletal muscle oxidative capacity (AvgRC textless 1.82) and high skeletal muscle oxidative capacity (AvgRC textgreater 2.13). Results: Participant characteristics including age, BMI, body fat percentage, handgrip, and skeletal muscle index (SMI) were similar between groups. SMOC was positively associated with myostatin at baseline (ß= 564.6, SE=232.4, p=0.045) and 24H following WBV (ß= 661.0, SE=189.4, p=0.029). In addition, a significantly higher overall myostatin (p=0.026) and IL-6 response (p=0.001) to WBV was observed in in the high skeletal muscle oxidative capacity group when compared to the low skeletal muscle oxidative capacity group. Conclusions: Higher skeletal muscle oxidative capacity is associated with a greater myostatin and IL-6 response to acute WBV. These data suggest that a higher SMOC at baseline may positively impact the myokine response to WBV, independent of adiposity, and demonstrates the importance of skeletal muscle health on preventing and ameliorating chronic disease.