Background: Sleep deprivation can decrease parental well-being and degrade mental and physical health in parents of children with chronic illness. The aim of this study was to explore the associations of sleep quality, psychological stress perception, and evening salivary cortisol concentration with self-esteem, optimism and happiness in parents of children with type 1 diabetes and developmental disorders compared to parents of healthy, typically developing children. Methods: We studied 196 parents of children with chronic conditions, including autistic spectrum disorder (N = 33), cerebral palsy (N = 18), Down syndrome (N = 33), and diabetes mellitus type 1 (N = 40) and parents of healthy children (N = 72). We evaluated parental sleep quality, evening salivary cortisol levels, self-esteem, optimism and happiness. Multiple linear regression models were used to assess associations between variables. Results: Compared with those of the control group, the parents of children with autistic spectrum disorders had higher evening cortisol concentrations ([beta] = 0.17; p = 0.038) and lower perceptions of happiness ([beta] =-0.17; p = 0.017), while parents of children with type 1 diabetes had disrupted sleep quality ([beta] = 0.25; p = 0.003). Optimism was negatively associated with the evening cortisol concentration ([beta] =-0.18; p = 0.023) and sleep quality index ([beta] =-0.20; p = 0.012). Conclusions: Public health programs aimed at lifestyle habit improvement, respite care, and relaxation for parents of children with chronic conditions would be useful for improving parental sleep quality, self-esteem, optimism and happiness.