Background: Children require a nurturing environment to develop optimally and reach their full potential. A critical component of this environment is the health and well-being of caregivers so that they can provide responsive caregiving. It is believed that parents or caregivers of children with ASD will have poorer health and well-being than parents or caregivers of children without ASD. Therefore, parents of children with ASD may require more support to enable them to provide responsive caregiving to these children. Methods: This study was a quantitative study that employed an analytical, comparative design. The purpose of this study is to determine if there is a significant difference in the health and well-being of parents with children with ASD and parents of children without ASD in the South African context. Two hundred and eight participants from two schools in Kwa-Zulu Natal completed a paper-based survey containing 3 questionnaires relating to health-related quality of life; stress, anxiety and depression and parental self-efficacy. Parenting constructs such as stress, anxiety and parental self-efficacy are measured and described, and the association between Health-related Quality of Life and constructs such as stress, anxiety and parental self-efficacy is explored. It took place at a special needs school in KZN and mainstream school in the same district. Results: The results of this study demonstrated a poorer HRQOL in some of the areas of parents of a child with ASD compared to parents of a child without ASD. The results from this study demonstrate the importance for health practitioners to focus on the parents' health and well-being as part of the child's intervention. Conclusion: Intervention is mainly child-focussed however it is important for practitioners to understand the caregiver's health and well-being as this will have a positive influence of the child and in turn, lead to successful intervention. It is therefore important to have a family-centred approach. The QOL of the parents or caregivers of children with ASD will improve through support and intervention which will positively impact on the child's development. If the caregiver is receiving the appropriate support, their QOL will improve and they will be able to provide nurturing care that the child needs.