AbstractDespite overlaps in clinical symptomatology, autism and ADHD may be associated with opposite autonomic arousal profiles which might partly explain altered cognitive and global functioning. We investigated autonomic arousal in 106 children/adolescents with autism, ADHD, co-occurring autism/ADHD, and neurotypical controls. Heart rate variability was recorded during resting-state, a ‘passive’ auditory oddball task and an ‘active’ response conflict task. Autistic children showed hyper-arousal during the active task, while those with ADHD showed hypo-arousal during resting-state and the passive task. Irrespective of diagnosis, children characterised by hyper-arousal showed more severe autistic symptomatology, increased anxiety and reduced global functioning than those displaying hypo-arousal, suggesting the importance of considering individual autonomic arousal profiles for differential diagnosis of autism/ADHD and when developing personalised interventions.