Context: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed medications to treat depression and anxiety. SSRIs exert their effects by inhibiting the serotonin transporter and modulating extracellular serotonin levels, a neurotransmitter that has been shown to affect bone metabolism in animals. Studies in adults suggest a negative association between SSRI use and bone mineral density (BMD), greater rates of bone loss with SSRI use and increased risk of fractures. However, the results on bone mass have been inconsistent. Furthermore, there is a dearth of studies examining an association between SSRI use and bone mass in the pediatric and adolescent age group. Objective: To investigate associations between SSRI use and bone mass in adolescents. Design: Cross-sectional analysis of data from the 2005-2010 National Health and Nutrition Examination Study (NHANES). Participants: 4303 NHANES participants aged 12-20. years. The mean age was 15.65 ± 2.42. years. Main outcomes: Total femur, femoral neck and lumbar spine bone mineral content (BMC) and BMD assessed via dual-energy X-ray absorptiometry (DXA). Results: 62 out of 4303 subjects used SSRIs. SSRI use was an independent predictor of bone mass after adjusting for age, gender, height and weight Z score, socioeconomic status, physical activity, serum cotinine level and race/ethnicity. After multivariable adjustment, total femur BMC was 8.8% lower among SSRI users versus non-users (mean difference 2.98 g, SE±0.105 g, p=0.0006), while total femur BMD was 6.1% lower (mean difference 0.06g/cm2, SE±0.002 g/cm2, p=0.016). Femoral neck BMC and BMD and lumbar spine BMC were similarly negatively associated with SSRI use. Compared to nonusers, lumbar spine BMC was 7% lower among SSRI users (mean difference 0.97 g, SE±0.048g, p=0.02) and BMD was 3.2% lower (mean difference 0.03 g/cm2, SE±0.015 g/cm2, p=0.09). Sub-analysis of those individuals treated for more than 6months yield similar results. Finally, the association of SSRIs with bone mass persisted after excluding individuals with Body Mass Index (BMI) less than 5th percentile thus accounting for the possible confounding effect of anorexia nervosa, which can be treated with SSRIs. Conclusion: In this NHANES study, adolescents treated with SSRIs had lower DXA measurements of the total femur and lumbar spine compared to SSRI non-users. These findings support the need for future prospective studies to examine the effects of SSRI use on bone mass in adolescents.