Background: Postural Orthostatic Tachycardia Syndrome (POTS) is associated with orthostatic intolerance manifested by an excessive heart rate rise with position change associated with multi-systemic symptoms of autonomic dysfunction. Patients can experience sudden clinical deterioration with any infectious stress. Evidence has shown COVID-19 to be an aggressive infection with serious consequences that can be ameliorated by the COVID-19 vaccination. The goal of this survey is to understand and identify the parental gaps in knowledge regarding the safety and efficacy of the COVID-19 vaccine, allowing healthcare professionals to better advocate, educate, and manage the needs of this vulnerable population. Methods: Parents of 203 pediatric POTS patients from a local group practice completed an online survey with a response rate of 37%. The survey focused on demographics, previous COVID-19 infection, vaccination, reason for vaccination, and knowledge of COVID-19. Results were analyzed using Chi-square test of independence to interpret the perception of COVID-19 illness and vaccine. Results: The results show 59% of patients are vaccinated, independent of sex, income, or education levels. Fear of side effects (37%) was the most common reason for not vaccinating. Almost no patients experienced side effects from the vaccine. More than half of surveys reported not receiving information from medical professionals on COVID-19. Conclusion: Lower vaccination rates highlight a fearful and negative perception of the COVID-19 vaccine despite no reported side effects in those vaccinated. Overall results demonstrate knowledge gaps regarding COVID-19 virus and vaccine. Education and advocacy are required from qualified sources to prevent significant morbidity in this already susceptible patient population.