ABSTRACT Recent reports from the American Journal of Public Health and the American Psychological Association identified a critical need to examine mechanisms by which exposure to psychosocial stress in childhood increases the risk for obesity and cardiovascular disease (CVD) in adulthood. Given there is a lag in time before the impact of psychosocial stress experienced in childhood is expressed as disease in adulthood, these calls-to-action urge researchers to investigate the role of modifiable factors over the course of childhood that may mitigate risk for later obesity and CVD. The proposed mixed-methods study is uniquely designed to answer these calls-to-action by examining how stress “gets under the skin” to put children at higher risk for later obesity and CVD, and ultimately health disparities by race/ethnicity. The main objectives of this study are to: (1) comprehensively examine the relationships between multi-level psychosocial stressors (i.e., individual, dyadic, household, societal) and their dimensions (i.e., severity, frequency, timing), biological factors (e.g., hypothalamic pituitary adrenal (HPA) axis activity), and child weight and emerging CVD risk over the course of childhood and (2) identify modifiable factors at the individual, parental, and familial level to interrupt these stress pathways. The proposed study will build on and expand a prior parent R01 study (HL126171). The parent R01 study is a two-phased, mixed-methods study including a prospective epidemiological cohort study with 1307 diverse parent/child (ages 5-16) dyads (≈200 each African American, Hispanic, Native American, Immigrant/Refugee, White) and an embedded ecological momentary assessment (EMA) sub-sample with 627 parent/child dyads (≈100 per each racial/ethnic group). Data was collected at two time points (baseline, 24-month follow-up). In the proposed study, online survey data and 7-day EMA data will be continued at 48 and 72 months, allowing for a total of four waves of data collection. Children, who are now ages 9-16 will be added to both the online survey and EMA data collection, in addition to participating in three 24 hr. dietary recalls and 7-day accelerometry. New biological measures (e.g., hair cortisol, body composition, arterial stiffness) with children and parents, neighborhood factors (e.g., child opportunity and disadvantage index) using geo-spatial measures, and societal-level factors (e.g., structural racism, sociopolitical shift, COVID-19) contributing to psychosocial stressors will also be added at both time points. Human-Centered Design multi-family focus groups will also be carried out to co-create intervention targets with families. This study will provide breadth and depth in understanding the pathways between multi-level psychosocial stressors and child weight and emerging CVD across important developmental milestones (e.g., puberty) and family life cycle stages (e.g., families with young children to families with adolescents). Import...