Excessive exposure to glucocorticoids causes osteoporosis in children and adults. Occlusal disharmony is known to induce an increase in serum corticosteroid levels in murine models, but the influence of occlusal disharmony-induced stress on the bone mass during the growth period has not yet been clarified. The purpose of this study was to investigate whether occlusal disharmony-induced stress decreases bone mass. Five-week-old C57BL/6J male mice were used. A 0.5-mm increase in the vertical height of occlusion was used to induce occlusal disharmony for a period of 7 days. Serum corticosterone levels were significantly higher on post-induction day 7, with radiological evidence of osteopenia of the third lumbar vertebra and long bones of the hind limbs. Osteopenia was associated with a reduction of the mechanical properties of the tibia and femur, with significant suppression of bone formation parameters and an increase in bone resorption parameters, as evaluated by bone histomorphometric analysis of the tibial/femur metaphysis. Our findings at the level of bones were supported by our assessment of serum markers of systemic metabolism. Therefore, occlusal disharmony-induced stress may lead to osteopenia and reduce the mechanical strength of bone through an increase in serum glucocorticoid levels in mice.