Social play and social interactions are essential occupations for children, but can be challenging for children with Autism Spectrum Disorders (ASD). This systematic review investigates cortisol responsivity in children with ASD during naturalistic social play and social interactions. Methodology: Six control and comparison studies of moderate quality were identified. Findings revealed that some children with ASD experience heightened stress (cortisol responsivity) during naturalistic social play and social interactions; however, this response is highly variable between individuals. These findings emphasize the importance of individualized approaches for children with ASD, to facilitate their engagement in these essential occupations.