Purpose: This study examined osteokines related to Wnt signaling at rest and in response to plyometric exercise in 12 boys [10.2 (0.4) y] and 12 girls [10.5 (0.4) y]. Methods: One resting (preexercise) and 3 postexercise (5 min, 1 h, and 24 h) blood samples were analyzed for sclerostin, dickkopf-related protein 1 (DKK-1), osteoprotegerin (OPG), and receptor activator of nuclear factor kappa-β ligand (RANKL). Results: Girls had higher resting sclerostin than boys [187.1 (40.1) vs 150.4 (36.4) pg·mL−1, respectively; P = .02]. However, boys had higher DKK-1 [427.7 (142.3) vs 292.8 (48.0) pg·mL−1, respectively; P = .02] and RANKL [3.9 (3.8) vs 1.0 (0.4) pg·mL−1, respectively; P < .01] than girls. In girls, sclerostin significantly decreased 5-minute and 1-hour postexercise (χ2 = 12.7, P = .01), and RANKL significantly decreased 5-minute postexercise (χ2 = 19.1, P < .01) and continued to decrease up to 24-hour postexercise, with large effect sizes. In boys, DKK-1 significantly decreased 1-hour postexercise and remained lower than preexercise 24-hour postexercise (χ2 = 13.0, P = .01). OPG increased in both boys (χ2 = 13.7, P < .01) and girls (χ2 = 11.4, P = .01), with boys having significantly higher OPG at 5-minute and 1-hour postexercise, whereas in girls, this increase was only seen 24-hour postexercise. Conclusion: Plyometric exercise induces an overall anabolic osteokine response favoring osteoblastogenesis over osteoclastogenesis in both boys and girls although the timeline and mechanism(s) may be different.