The aim of the present study was to assess parenting stress during the COVID-19 pandemic in Greece. The impact of COVID-19 outbreak on parental stress is substantial, and those caring for children with underlying disorders are more profoundly affected. Pending the global socioeconomic rebooting after the pandemic, the possible short- and long-term consequences of parental stress should not be ignored. As for other vulnerable groups, accurate health information and resources for psychological support should be provided to parents, especially those caring for children with underlying disorders.