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Depression and obesity are both important public health problems. However, it is not clear whether obesity contributes to depression. Our study aims to evaluate the association between obesity and possible depression.During the Beaver Dam Offspring Study examination, participants' body weight and height were measured with a Detecto 758C digital scale with height bar, and depression symptoms were measured with the Center for Epidemiological Studies-Depression (CES-D) Scale. Other relevant information, such as demographic factors, lifestyle factors, comorbidities, and use of antidepressants, was also collected during the examination. There were 2,641 participants included in the analyses.Obesity was associated with possible depression measured by CES-D Scale (OR=1.6, 95% CI: 1.3–2.0) after controlling for age and gender. The association remained similar after further adjustments. Obesity was significantly associated with all four domains measured by CES-D Scale after controlling for age and sex, with the largest effect on “Somatic Complaints” domain (β .15, 95% CI: 0.0836–0.223). The association with “Interpersonal Difficulties” was not significant after further adjustments.Obesity was associated with a higher risk of possible depression and had different influences on specific domains of depression symptoms measured by CES-D Scale. These findings suggest the need for longitudinal studies on the effects of obesity on specific depression symptoms.