Abstract: Background: Puerto Rico and U.S. Virgin Islands Veterans (PRs) have faced recurring challenges from hurricanes, earthquakes, and the COVID-19 pandemic. These events combined with prior traumas and social determinants of health (SDoH), may contribute to neuropsychiatric mental health conditions (MHCs) like post-traumatic stress disorder (PTSD) and substance use disorder (SUD) in PRVs affected by SARS-CoV-2. Methods: To clinically characterize the risk factors for MHCs among SARS-CoV-2 infected PRVs, we examined 839 records (2016-2020) to study SARS-CoV-2 infections and MHCs. Records were assessed for (i) PTSD and SUD using health data at diagnosis; (ii) clinical details pre-hurricanes (control; group 1), during hurricanes (group 2), and pandemic (group 3). Groups 1 and 2 were reviewed in 2020 to gauge exacerbation. Patient Health Questionnaire (PHQ-2/PHQ-9), PTSD checklist (PCL-5), Alcohol Use Disorders Identification Test (AUDIT), SDoH, and other tools were used for clinical evaluation, with the data analyzed using logistic regression. Results: Health data indicated SARS-CoV-2 infection in 21 PRVs. Earthquakes did not affect the infected PRVs nor did SDoH have any significant impact. Clinical analysis revealed that SUD worsened during hurricanes and exacerbation of all MHCs occurred during the pandemic among SARS-CoV-2 infected PRVs. Conclusions: These results underscore the fact that the combination of natural disasters like hurricanes and SARS-CoV-2 had synergistically contributed to the deterioration of neuropsychiatric MHCs, therefore warranting equitable MH support.