Background: Ghrelin, leptin and high-molecular-weight (HMW) adiponectin have been linked to depression in middle-aged adults. Pathophysiological mechanisms of depression change as age progresses and it is unclear whether the same associations exist in older adults. Methods: We analyzed the associations between ghrelin, leptin and HMW adiponectin and depressive symptoms (Center for Epidemiologic Studies Depression (CES-D) score ≥ 16) in a community-dwelling cohort of 898 participants in a multivariable logistic regression analysis at baseline and after three years of follow-up, were applicable stratified by sex, age and waist-hip-ratio (WHR). Results: At baseline no significant associations were found. After three years of follow-up ghrelin was associated with higher odds for depressive symptoms (fully adjusted continuous analysis OR 2.27, 95% CI 1.42 – 3.61). There was effect modification for age and WHR, with significant associations in participants younger than 69.7 years (median) and with a WHR below 0.9554 (mean). In the sex-stratified analysis for leptin we found significant associations in men (fully adjusted continuous analysis OR 1.07, 95% CI 1.02 – 1.12). For HMW adiponectin there were no significant associations in the multivariable analysis. Limitations: As our cohort consisted of relatively healthy participants with intact cognitive function, selection bias may have contributed to lack of significant baseline associations. Conclusions: Our results show significant associations between ghrelin and – for men only - leptin and depressive symptoms after three years of follow up. This may provide a new therapeutic window for treatment of depressive symptoms in older adults, as both ghrelin and leptin are positively influenced by weight loss.