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Inflammation has been implicated in the pathogenesis and maintenance of depressive symptoms. The role of inflammation in depressive symptomatology may be complex, varying within endophenotypes and across the lifespan. Aging is associated with myriad changes in the structure and function of the brain. Yet, little attention has been given to the role of inflammation in depressive symptoms within a lifespan developmental framework. In this study, we examined whether the association between inflammation and depressive symptom domains varied by age. Participants were a community sample of individuals (N = 2,077, Range = 30–84) who participated in the Biomarker projects of the MIDUS2, MIDUS Refresher, or the MIDJA study. Inflammation was indexed by two inflammatory markers consistently implicated in depressed individuals, interleukin 6 (IL-6) and C-reactive protein (CRP), measured in blood. Depressive symptom domains, including depressed affect, anhedonia, somatic complaints, and interpersonal problems, were reported via the Center for Epidemiologic Studies—Depression Scale (CES-D). Inflammatory markers were associated with more somatic complaints, more interpersonal problems, and less anhedonia. Age moderated the relationship between inflammatory markers and two depressive symptom subscales. Specifically, the positive association between inflammation and somatic complaints and the negative association between inflammation and anhedonia increased with age. These observations offer preliminary evidence from a large community sample that aging may be an important context for the role of inflammatory signaling in different aspects of psychological and behavioral well-being.