Objective: This study investigated the impact of COVID-19 home confinement on autism spectrum disorder (ASD) symptoms and irritability in children and adolescents with ASD. Method: The study participants included 46 drug-naive children aged 4-17 years diagnosed with ASD. Parents of the participants completed the Autism Behaviour Checklist (AuBC) and Affective Reactivity Index (ARI) scales for both normal conditions and COVID-19 home confinement. Results: All subscale scores for AuBC (sensory, relating, body and object use, language, and social and self-help) and ARI scores significantly increased during the COVID-19 home confinement period (P <.05). The participants’ irritability and ASD symptoms were significantly worse during the COVID-19 outbreak and home confinement period compared to normal conditions. The variables that predicted irritability were the social and self-help subscales of AuBC. Discussion: These results have alerted us of the importance of focusing on the symptoms such as irritability exhibited by extremely vulnerable populations during disease outbreaks and of the necessity of developing new strategies to avoid such adverse outcomes in similar situations.