Background: This study investigated the impact of stress on levels of depression and ill health as an indication of psychological coping. The research sample consisted of 80 family caregivers (who are members of Headway Gauteng, located in Johannesburg, South Africa) of patients with acquired brain injury.; Methods: A mixed method design of data collection was utilised that included self-report procedures (structured questionnaires and interviews) and post-interview content analyses. In addition, two individually administered measures that have been widely used in clinical practice and research were administered (a stress symptom checklist and the Beck Depression Inventory).; Results: The majority of the research participants experienced high levels of stress along with an inordinate physical and mental health impact indicating that they were not able to cope up with the ongoing chronic stress of caregiving.; Conclusion: Findings provide compelling evidence of the value of psychological screening for elevated stress and poor coping in family members caring for a patient with acquired brain injury in a resource-limited healthcare society. We recommend a collaborative effort between medical and psychological health practitioners in order to ensure a holistic and inclusive approach towards treatment procedures and interventions to improve coping skills in family members caring for a patient with acquired brain injury.