The relation of the cumulative experience of poverty in infancy and early childhood to child cortisol at age 48 months was examined in a prospective longitudinal sample of children and families (N=1292) in predominantly low-income and rural communities in two distinct regions of the United States. Families were seen in the home for data collection and cumulative experience of poverty was indexed by parent reported income-to-need ratio and household chaos measures collected between child ages 2 months and 48 months. For the analysis presented here, three saliva samples were also collected over an approximate 90 min interval at child age 48 months and were assayed for cortisol. ECG data were also collected during a resting period and during the administration of a mildly challenging battery of cognitive tasks. Mixed model analysis indicated that child cortisol at 48 months decreased significantly over the sampling time period and that cumulative time in poverty (number of years income-to-need less than or equal to 1) and cumulative household chaos were significantly related to a flatter trajectory for cortisol change and to an overall higher level of cortisol, respectively. Findings also indicated that respiratory sinus arrhythmia derived from the ECG data moderated the association between household chaos and child cortisol and that increase in respiratory sinus arrhythmia during the cognitive task was associated with an overall lower level of cortisol at 48 months.