Background: Over the last several decades, the prevalence of Autism Spectrum Disorder (ASD) has continued to increase, creating a unique challenge for general physicians who are likely to encounter these patients in their practice. The primary aim of this cross-sectional study design was to identify potential knowledge gaps that were present among medical students and pediatric trainees (interns, residents, and fellows) particularly during the management of a sick child with ASD. Methods: A 23-question online survey was developed and distributed to medical students and pediatric trainees at a tertiary children's hospital affiliated with a medical school. Results: Medical students and pediatric trainees reported a low general knowledge of ASD and were unfamiliar with sensory issues that is often present in these children. Increased discomfort and insufficient didactic and clinical training for providing care to children with ASD during an acute illness were also identified. Both medical students and trainees reported the need for increased education and training, preferentially via patient interaction and small group-based learning. We found that as education/training levels increased, participants perceived increased comfort and knowledge in managing an ill child with ASD. Conclusions: A perceived knowledge gap and discomfort is present amongst medical students and pediatric trainees on the management of children with ASD. Across all education levels, awareness for sensory dysregulation in ASD children is low. Education programs using direct patient interaction and small group learning were the preferred training modalities to learn how to provide optimal care for children with ASD.