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The COVID-19 lockdown affected children, especially those with autism spectrum disorder, due to the disruption in rehabilitation and educational activities. We conducted a cross-sectional study of 315 preschool-aged children, 35 of which had autism, to investigate this impact. A questionnaire was administered to explore socio-demographic status, familiar/home environment, and COVID-19 exposure. The clinical features of autistic subjects were also examined. Seven variables were considered to describe the effect of pandemic: Remote learning, Behavior changes, Home activities, Sleep habits, Night awakenings, Physical activity, Information about the virus. The lockdown had a significant impact on Remote learning, Behavior changes, and Information about the virus in participants with autism. Moreover, we found a worsening in repetitive movements, echolalia, restricted interests, and aggressive behaviors.