Biological and epidemiological evidence has linked early-life psychosocial stress with late-life health, with inflammation as a potential mechanism. We report here the association between familial death in childhood and adulthood and increased levels of high-sensitivity C-reactive protein (CRP), a marker of systemic inflammation. The Cache County Memory Study is a prospective study of persons initially aged 65 and older in 1995. In 2002, there were 1,955 persons in the study with data on CRP (42.3 percent male, mean [SD] age = 81.2 [5.8] years), linked with objective data on family member deaths. Using logistic regression, high (> 10 mg/L) versus low (≤ 10 mg/L) CRP was regressed on cumulative parental, sibling, spouse, and offspring deaths during childhood and during early adulthood, adjusted for family size in each period (percentage family depletion; PFD). Findings revealed PFD during childhood to be significantly associated with CRP (OR = 1.02, 95% CI [1.01, 1.04]). Individuals with two or more family deaths were 79 percent more likely to have elevated CRP than those with zero family deaths (OR = 1.79, 95% CI [1.07, 2.99]). Early adulthood PFD was not related to CRP. This study demonstrates a link between significant psychosocial stress in early life and immune-inflammatory functioning in late life, and suggests a mechanism explaining the link between early-life adversity and late-life health.