To determine which factors are highly associated with burden and depression in a group of caregivers of persons with Traumatic Brain Injury (TBI) in Colombia, South America.Prospective.Fifty-one pairs of individuals with TBI and their caregivers from two major cities in Colombia completed a comprehensive psychosocial evaluation that included information related to patient and caregiver sociodemographic factors, patient factors, and caregiver estimation of patient neurobehavioral functioning.Caregiver burden (Zarit Burden Interview) and caregiver depression (PHQ-9).Generalized linear models revealed that patient language problems and caregiver perception of patient functioning on six neurobehavioral domains were related to caregiver burden. Caregiver socioeconomic status and caregiver perception of patient functioning on six neurobehavioral domains were related to caregiver depression. These variables were then selected as candidates for the multiple regression models, which were fit separately for caregiver depression and burden, and revealed that caregivers' perception of patient depression was the only factor associated with both caregiver burden and depression.Caregivers' perception of patient depression was the single best predictor of both caregiver burden and depression. Implications for treatment based on these preliminary findings are discussed.