Children (N = 324 boys, 315 girls) between the ages of 2.5 and 6 (mean age = 3.63) were identified in a house to house survey in low-income areas (income <20th percentile nationally) of urban Mexico. The Center for Epidemiologic Studies—Depression Scale was administered to mothers of all children. Salivary cortisol samples were taken in children as a measure of hypothalamic–pituitary–adrenocortical (HPA) system activity at time of arrival (baseline, Time 0), 25 min after arrival (Time 1), and 50 min after arrival (Time 2). Between Time 0 and Time 1, children were administered several cognitive tests. Results of hierarchical linear modeling analyses revealed that higher levels of maternal depressive symptoms were associated with lower baseline cortisol levels in their children (p < .05), while controlling for age, gender, and time since awakening. Higher levels of maternal depressive symptoms were associated with less of an increase in salivary cortisol to the arrival of the experimenters and subsequent cognitive testing (p < .05). All results were moderated by gender, with enhanced cortisol response in girls and no response in boys. These results suggest that among very low-income families, high maternal depressive symptoms are associated with hypoactivity of the HPA system in children, particularly boys.