Background: Previously, we found that reported infant rhinorrhea and watery eyes without a cold (RWWC) predicted school age exercise-induced wheezing, emergency department visits, and respiratory-related hospitalizations for asthma. These findings appeared independent of infant wheezing and allergy. Overall, we theorize that prenatal material hardship and psychosocial distress can induce infant dysregulation in the autonomic nervous system leading to infant RWWC and school age exercise-induced wheezing. Objective: To test the hypotheses that indicators of prenatal stress and measures of maternal demoralization, which can alter infant autonomic nervous system responses, would predict infant RWWC. Methods: In a prospective birth cohort of urban children (n = 578), pregnant women were queried in the third trimester about material hardship and maternal demoralization using validated instruments. Child RWWC was queried every 3 months in infancy. Results: Notably, 44% of the mothers reported not being able to afford at least one of the basic needs of daily living during pregnancy, and children of those mothers were more likely to have infant RWWC (P < .001). The children had an increased risk of RWWC with increasing maternal demoralization during pregnancy (P < .001). In models controlling for sex, race and ethnicity, maternal asthma, maternal allergy, smoker in the home (pre- or postnatal), prenatal pesticide exposure, and older siblings, RWWC was predicted by mother's report of material hardship (relative risk, 1.22; P = .021) and maternal demoralization (relative risk, 1.14; P = .030). Conclusion: These results suggest an association between material hardship and psychological distress during pregnancy and RWWC in infancy, further supporting a link between infant autonomic dysregulation and RWWC.