ABSTRACTWomen in urban neighborhoods often face disproportionately higher levels of environmental and social stressors; however, the health effects from urban stressors remain poorly understood. We evaluated the association between urban stress and depression, fatigue, and sleep disruption in a cohort of 460 women in Mexico City. To assess urban stress, women were administered the Urban Annoyances scale. Six constructs were summarized to create an overall index. Depressive symptoms were assessed using the Edinburgh Depression Scale; the Patient-Reported Outcomes Information System scales were used to assess sleep disruption and fatigue. Linear regression models were used to estimate the association with continuous symptoms comparing women with high stress to those with lower levels. Models were adjusted for socioeconomic status, education, age, social support, and previous depressive symptoms. High urban stress was associated with greater depressive symptoms (β: 1.77; 95% CI: 0.83, 2.71), fatigue (β: 2.47; 95% CI: 0.87, 4.07), and sleep disruption (β: 2.14; 95% CI: 0.54, 3.73). Urban stress plays an important role in women’s psychological and physical health, highlighting the importance of including these measures in environmental health studies. Urban interventions, such as promoting alternative transport options, should additionally be addressed to improve health of urban populations.