OBJECTIVES: To evaluate the association between adverse experiences during Hurricane María and mental and emotional distress in Puerto Rico. METHODS: This cross-sectional study used baseline data from adult (30-75 years) participants of the Puerto Rico Observational Study of Psychosocial, Environmental, and Chronic Disease Trends (PROSPECT). Enrolled individuals prior to COVID-19 who completed a 33-item questionnaire on Hurricane María-related experiences (sub-categorized as personal, service, or property losses), depression symptomatology, post-traumatic stress disorder (PTSD), and anxiety were included for analysis (n = 456). RESULTS: Most participants experienced fear for their family's safety, damage to their home and personal items, communication outages, and water shortages. Each additional stressor was significantly associated with higher odds of depression symptoms, PTSD, and anxiety. Personal losses were significantly associated with higher likelihood of all outcomes, while services losses were associated with depression symptoms and anxiety; property loss was not significantly associated with any outcome. CONCLUSIONS: Adverse experiences during a major natural disaster are associated with mental and emotional distress. Strategies to minimize hardships during natural disasters, especially personal and service losses, are essential to preserve mental health. Post-disaster psychological support to individuals is crucial.