Objectives: Previous researches have investigated depression in postmenopausal women (PMW) with osteoporosis and fractures, but little is known regarding Moroccan PMW without fractures. We investigated depression prevalence and severity in Moroccan PMW with osteoporosis without fractures and its relationship with quality of life (QoL) and physical and psychological state. Methods: This cross-sectional study enrolled 100 PMW with osteoporosis without fractures. Depressive symptoms, QoL, self-esteem, and fatigue were evaluated using the Patient Health Questionnaire-9 (PHQ-9), Arabic version of ECOS-16 questionnaire, Rosenberg self-esteem scale, and Arabic version of the Multidimensional Assessment of Fatigue scale, respectively. A questionnaire including sociodemographic factors, bone density features, pain intensity, and sleep disturbance was completed. Results: Overall, 58% patients suffered from depression and 55% from pain (63.8% depressed women vs. 42.9% nondepressed patients; P = 0.03). Bone mineral density, lumbar spine T-score, ECOS-16, and self-esteem in depressed and nondepressed women were 0.791 (0.738–0.840) vs. 0.835 (0.790–0.866); –3.25 (–3.8 to –2.875) vs. –2.9 (–3.425 to –2.700), P= 0.02; 2.338 ± 0.605 vs. 1.638 ± 0.455;and 13.517 ± 5.487 vs. 18.404 ± 5.771, P < 0.0001, respectively. Depression severity correlated with pain, QoL, self-esteem, and fatigue (r = 0.367, r = –0.390, r = –0.390, and r = 0.369, respectively; P< 0.0001) as well as lumbar spine bone mineral density and T-score (r = –0.258 and r = –0.255, respectively; P = 0.01). Multiple linear regression analysis revealed impaired QoL (β = 0.526; P < 0.0001), fatigue (β = 0.177; P= 0.02), and lower self-esteem (β = –2.170 P = 0.005) as the strongest risk factors of depression. Conclusions Our study shows that even without fractures, Moroccan PMW with osteoporosis suffered from depression, pain, impaired QoL, and lower self-esteem.