Background: Parents of children with autism spectrum disorder (ASD) present more wellbeing and stress problems than parents of typically developing (TD) children. However not all parents present these problems. These problems can be due to a dynamic interaction between environmental antecedents, person antecedents, and mediating processes. Understanding how these factors separately contribute to explain parents' well-being and stress can have implications for intervention programs. The aim of this study was to explain parents' subjective well-being and physiological stress by considering whether they had a child with ASD or not and their child's negativity (environmental antecedents), their perception of their child's problems (person antecedents), and their use of reappraisal (mediating processes). Method: Thirty-seven parents of children with ASD and 41 parents of TD children reported their subjective well-being and their physiological stress was assessed. Additionally, children's negativity was observed, parents rated their perception of their child's problems (autistic traits, emotion regulation ability, and lability/negativity), and parents reported their use of reappraisal. Results: Compared to parents of TD children, parents of children with ASD reported having lower subjective well-being and had increased physiological stress. Parents' perceptions of children's lability/negativity and parents' use of reappraisal were better predictors of parents' subjective well-being than ASD and parents' perceptions of children's lability/negativity contributed to parents' physiological stress as much as ASD. Conclusions: Prevention and intervention programs targeting parental well-being and stress will benefit from working with parents at the level of perceptual constructs and reappraisal ability. (C) 2017 Elsevier Ltd. All rights reserved.