The effect of plyometric exercise on bone biomarkers has been studied in pediatric and young adult populations in order to better understand how exercise influences bone homeostasis. However, there are no such data in postmenopausal women, a group characterized by an uncoupling of the bone resorption-formation cycle. This study examined the serum concentrations of sclerostin, dickkopf-1 (DKK1), c-terminal crosslinking telopeptides of type I collagen (CTXI), and procollagen type I amino-terminal propeptide (PINP) at rest and following a single bout of plyometric exercise in 20 premenopausal (23.1 ± 2.3 years) and 20 postmenopausal women (57.9 ± 4.3 years). The exercise consisted of 128 jumps, organized into 5 circuit stations. Blood samples were obtained prior to and 5 min, 1 h, and 24 h postexercise. At rest, postmenopausal women had significantly higher sclerostin and CTXI, but lower DKK1 than premenopausal women. Sclerostin increased 5 min postexercise only in the premenopausal group. DKK1 decreased 24 h postexercise in the premenopausal women while it decreased 1 h postexercise in the postmenopausal women. In both groups, CTXI did not change across time and PINP decreased 5 min and 1 h postexercise (p < 0.05). The PINP/CTXI ratio decreased 5 min and 1 h postexercise then significantly increased 24 h postexercise only in premenopausal women. These results indicate that although plyometric exercise is effective in eliciting osteoanabolic effects in younger women; such an effect is not evident in postmenopausal women.