OBJECTIVE: The present study aimed to test the role of the autonomic nervous system (ANS) in modulating the impact of family stress induced by harsh parenting on youths\' inflammation. First, we examined the direct effect of severity of adverse parenting behaviors on two serum biomarkers of systemic inflammation (C-reactive protein and interleukin-6) among youth. Second, we tested the moderating role of ANS reactivity in response to laboratory-induced stress in the association between harsh parenting and inflammation among these youth. METHOD: The sample included 101 low-income children (75.2% African American) between 9 and 12 years of age (M(age) = 10.9; SD(age) = 1.2) who participated in a conflict task with their primary caregiver in a laboratory setting. Heart rate variability reactivity (HRV-R), skin conductance level reactivity (SCL-R), and preejection period reactivity (PEPr-R) were used to index parasympathetic and sympathetic nervous system reactivity. Markers of low-grade inflammation (C-reactive protein and interleukin-6) were obtained from serum. RESULTS: After adjusting for confounding variables, ANS activity moderated the associations between family stress and systemic inflammation. Specifically, elevated HRV-R buffered the effect of family stress on youths\' inflammation, whereas elevated PEPr-R and SCL-R exacerbated the effect. CONCLUSION: These findings show that self-regulatory capacity and threat sensitivity, as indicated by ANS function, may have an impact on the associations between family stress and systemic inflammation. (PsycInfo Database Record (c) 2020 APA, all rights reserved).