Background This study explored the synergistic relationship between stigma, self-esteem and social support, as predictors of depressive symptomology in parents of children with disabilities (e.g. Autism and Down syndrome).Method One hundred and seventy-three parents (115 parents of children with disabilities and 58 control parents) completed measures of perceived stigma, self-esteem, social support and depressive symptoms. Results Parents of children with disabilities reported more depressive symptomology; additionally, stigma, self-esteem and social support were associated with depressive symptomology. Moreover, the association between stigma and depressive symptomology was mediated by self-esteem, i.e. parents who reported higher stigma were lower on self-esteem and more depressed. Further, this path varied as a function of emotional support.Conclusion Results highlight the need for tailored interventions that offer parents effective strategies in dealing with stigma through social support and self-esteem.