Background/objectives Aging-related physiological changes like metabolic dysregulation and physical frailty are associated with depression and worsen its prognosis. Since central obesity is a key component of the metabolic syndrome and sarcopenia of physical frailty, we examined the association of sarcopenic obesity with depression cross-sectional and over time. Methods Cohort study of depressed patients and a nondepressed comparison group. Setting Primary and secondary mental health care. Participants Three hundred seventy-eight older (>= 60 y) depressed patients of which 285 were followed up at 2 years and 132 nondepressed persons participating in the Netherlands Study of Depression in Older (NESDO) persons. Measurements Sarcopenic obesity was based on predefined cutoffs for both maximum handgrip strength (assessed with a dynamometer) and waist circumference (dichotomous) as well as the product term of handgrip strength by waist circumference (dimensional). Depressive disorder according to DSM-IV-TR criteria was assessed with fully structured psychiatric interview at baseline and 2-year follow-up. Results Sarcopenic obesity was more prevalent among depressed patients compared with nondepressed participants (18.9% versus 10.7%, P = 0.030). Neither the dichotomous nor dimensional operationalization of sarcopenic obesity was associated with baseline depressive disorder when adjusted for covariates. Nonetheless, among depressed patients, logistic regression showed that the interaction of handgrip strength by waist circumference was associated with remitted depression at 2-year follow-up (P = 0.044). Only among patients with a low handgrip strength, a higher waist circumference predicted nonremission. Conclusion Among depressed patients, sarcopenic obesity predicts nonremission of depression. Therefore, combined exercise and nutritional interventions might be effective for depressed patients with sarcopenic obesity.