The cross-sectional area of total muscle mass has been reported to decrease by about 40% for those 20-60 years of age. Depressive symptoms may discourage motivation to engage in physical activity such as strength training shown to negate muscle loss. Inflammation related to depressive symptoms may also contribute to muscle atrophy. Physiological differences by sex and race/ethnicity may also modify the association between depression and muscle mass. Evidence on the relationship between depression (or depressive symptoms) and adiposity has been mounting; however, little is known about the depressive symptoms-muscle mass association. We sought to determine the association between elevated depressive symptoms (EDS) and lean muscle mass and whether this varies by sex and race/ethnicity.Evaluating 1605 adults (45-84 years of age) from the Multi-ethnic Study of Atherosclerosis Abdominal Body Composition, Inflammation and Cardiovascular Disease Study, we examined the cross-sectional association between EDS (Center for Epidemiologic Studies for Depression Scale score≥16 and/or antidepressant use) and computed tomography-measured abdominal lean muscle mass using linear regression. Muscles were evaluated as a whole and by functionality (locomotion vs. stabilization/posture). Covariates included height, body mass index, sociodemographics, comorbidities, inflammatory markers and health behaviors (pack-years of smoking, alcohol locomotion compared to men, total intentional exercise, daily caloric intake). Sex and race/ethnicity were assessed as potential modifiers. Statistical significance was at a p<0.05 for main effects and <0.20 for interaction.Men with elevated depressive symptoms had 5.9 cm2 lower lean muscle mass for locomotion compared to men without EDS, fully-adjusted (CI=-10.5, -1.4, p=0.011). This was statistically significantly different from the null finding among women (interaction p=0.05). Chinese participants with EDS had 10.2 cm2 lower abdominal lean muscle mass for locomotion compared to those without EDS (fully-adjusted, CI=-18.3, -2.1, p=0.014), which was significantly different from the null relationship among White participants (interaction p=0.04). No association was observed between elevated depressive symptoms and muscle for stabilization/posture evaluating the whole population or stratified by sex or race/ethnicity.In the presence of elevated depressive symptoms, men and Chinese participants may have lower muscle mass, particularly for locomotion.