Despite the body of research on caregivers of individuals with various types of disabilities, SCI caregivers have received comparably less attention, especially in regions like Latin America.The purpose of this study was to examine the association between HRQOL and mental health in SCI caregivers from Colombia.A cross sectional study assessed SCI caregivers (n = 40) in Neiva, Colombia. Participants completed a measure of their HRQOL (SF-36 Health Questionnaire) and four measures of mental health (Satisfaction With Life Scale, Zarit Burden Interview, Patient Health Questionnaire-9, and State-Trait Anxiety Inventory).A canonical correlation between variables revealed that 64% of the variance was shared between mental health and HRQOL. The domains that loaded highest within the canonical correlation were social functioning, general health, and anxiety, indicating that SCI caregivers with higher anxiety experienced lower social functioning and lower general health. Furthermore, 15 of the 24 bivariate correlations between mental health and HRQOL were statistically significant, suggesting a strong connection between these two sets of variables.Rehabilitation professionals in Latin America should consider the development of caregiver interventions focusing on both physical and mental health, as the two constructs are closely connected through social functioning, general health, and anxiety.