Latin America has high rates of traumatic brain injury (TBI), yet reduced mental and physical health outcomes due to limited rehabilitation services. To understand the psychosocial adjustment process in TBI patients in Latin America, the incorporation of cultural values including family-based variables is imperative. The current study examined relations among healthy family dynamics, coping, and mental and physical health related quality of life (HRQL) among a sample of TBI patients across three sites and two countries over the first 4 months post-injury. A sample of 109 acute TBI patients from Mexico and Colombia were recruited, and a series of longitudinal mediation and cross-lag panel analyses were run. Mental and physical HRQL were positively associated with each other, as well as healthy family dynamics and coping. Coping partially mediated the effects of healthy family dynamics on both mental and physical HRQL. Family dynamics showed the strongest cross-lag relationships with coping going from 2 months to 4 months. Similarly, coping showed the strongest cross-lag relationships with both mental and physical HRQL going from baseline to 2 months. Results provide empirical support for the importance of a rehabilitation workforce that has been trained in and can effectively implement family-based interventions for individuals with TBI in Latin America.