Previous research has examined the health-related quality of life (HRQOL) and mental health of persons with spinal cord injury (SCI), but the majority of the research has taken place in the United States, Western Europe, and other developed countries. Limited research has been conducted with persons with SCI in Latin America.To examine the relationship between HRQOL and mental health in persons with SCI from Neiva, Colombia.Cross-sectional.Participants were recruited from the Foundation for the Integral Development of People with Disabilities, a nonprofit community organization for persons with disabilities.Forty persons with SCI from Neiva, Colombia.Caregivers completed the Spanish versions of questionnaires.Participants completed self-report measures of HRQOL (SF-36 Health Questionnaire) and mental health (Satisfaction with Life Scale, Patient Health Questionnaire-9, and State Trait Anxiety Inventory).The hypothesis that higher HRQOL would be related to better mental health found robust support, as the canonical correlation between these 2 sets of variables uncovered that 50.4% of the variance was shared, such that persons with lower HRQOL had reduced mental health. Within this canonical correlation, anxiety, fatigue, and general health loaded most highly, suggesting that persons with SCI who experienced lower energy and reduced general health tended to have high anxiety. Additionally, 9 out of the 18 bivariate correlations between these 2 variable sets were statistically significant.In Latin America, SCI rehabilitation services are extremely sparse and rarely include interventions that target postinjury mental health. The current study suggests that mental health issues in patients with reduced HRQOL warrant attention in SCI rehabilitation services, especially in this region.