BACKGROUND: Previous studies have found that exposure to childhood environmental stress is associated with cardiometabolic risk. However, it is not known whether individual health behaviors disrupt this relationship. This study prospectively evaluated the relationship between cumulative environmental stress in a low-income sample and cardiometabolic risk in middle childhood and examined whether child health behaviors attenuated this relationship. METHODS AND RESULTS: In a cohort of children (n=338; 57% Hispanic children; 25% Black children), environmental stressors (family and neighborhood factors representing disadvantage/deprivation) and child health behaviors (accelerometry measured physical activity; parent-reported screen time and diet recalls) were measured over 5 time points beginning when children were aged 2 to 4 years and ending when they were aged 7 to 11 years. Children's cardiometabolic risk factors (body mass index, blood pressure, triglyceride/high-density lipoprotein ratio, glucose, hemoglobin A(1c), C-reactive protein) were measured at 7 to 11 years. Emerging cardiometabolic risk was defined as having ≥ 1 elevations that exceeded clinical thresholds. In adjusted path analyses, greater cumulative environmental stress was associated with higher likelihood of emerging cardiometabolic risk in middle childhood (P<0.001). Higher levels of moderate to vigorous physical activity and fewer sedentary minutes attenuated the positive relationship between stress and cardiometabolic risk (P<0.05). Children with >2 hours of average daily screen time had a higher likelihood of elevated cardiometabolic risk (P<0.01), but screen time did not moderate the stress-cardiometabolic risk relationship. Dietary intake was not related to cardiometabolic risk. CONCLUSIONS: Interventions that promote moderate to vigorous physical activity and limit sedentary behavior may have particular importance for the cardiometabolic health of children exposed to high levels of cumulative environmental stress.