Background: Patients with major depression have elevated levels of inflammatory cytokines. We examined the link between inflammatory markers and depressed mood in a community-based sample of older people. Methods: Data are from 3024 well-functioning older persons, 70-79 years of age, participating in the Health, Aging and Body Composition study. Depressed mood was defined as a Center for Epidemiologic Studies Depression scale score of 16 or higher. Plasma concentrations of interleukin (IL)-6, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP) were measured. Results: Compared with the 2879 nondepressed subjects, the 145 persons with depressed mood had higher median plasma levels of IL-6 (2.04 vs. 1.83 pg/mL, p = .02), TNF-α (3.43 vs. 3. 16 pg/mL, p = .05), and CRP (1.96 vs. 1.66 mg/L, p = .03). After adjustment for health and demographic variables, depressed mood was especially prevalent among persons who had a high (above median) plasma level for at least two of the inflammatory markers. Compared with those without high levels, for persons with a high level for two or all three markers the risk of depressed mood was 2.45 (95% confidence interval [CI] = 1.34-4.47) and 2.40 (95% CI = 1.27-4.53), respectively. The association between depressed mood and serum level of IL-6 was significantly stronger in men than in women. Conclusions: In old age, depressed mood is associated with high levels of inflammatory markers, suggesting that depressed mood is causing and/or caused by systemic inflammation.