Early adversity has been shown to sensitize individuals to the effects of later stress and enhance risk of psychopathology. Using a longitudinal randomized trial of foster care as an alternative to institutional care, we extend the stress sensitization hypothesis to examine whether early institutional rearing sensitizes individuals to stressful events in adolescence engendering chronic low-grade inflammation. At baseline, institutionalized children in Romania (ages 6–31 months) were randomly assigned to foster care or to remain in usual care within institutions. A group of never-institutionalized children was recruited as an in-country comparison sample. At ages 12 and 16, participants reported stressful events. At age 16, Interleukin-6 (IL-6) and C-reactive protein (CRP) were derived from blood spots. Among children assigned to care as usual, more stressful events at age 12, but not age 16, were associated with higher IL-6. In the same group, stressful events at age 16 were associated with higher CRP, though these effects attenuated after adjusting for covariates. These associations were not observed in the foster care or never-institutionalized groups. The findings suggest that heightened inflammation following stress exposure is one pathway through which early neglect could compromise physical health. In contrast, early family care might buffer against these risks.