The coronavirus disease 2019 (COVID-19) pandemic has affected people worldwide, and pediatric patients with underlying diseases are at high risk of developing severe COVID-19. However, there are limited reports on the clinical impact of COVID-19, especially in patients with underlying neuromuscular diseases (NMD) and inborn errors of metabolism (IEM). This study aimed to investigate the incidence and clinical presentation of COVID-19 in patients with NMD and IEM. This was a single-center, cross-sectional study of patients with NMD and IEM in Japan for 2 years, from April 1, 2020 to March 31, 2022. Among 255 participants with a median age of 14 (range: 0-50) years, 192 (75%) and 63 (25%) had NMD and IEM, respectively. Among 255 patients, 8 (5 NMD and 3 IEM) were positive for the anti-severe acute respiratory syndrome coronavirus 2 nucleocapsid antibody, and the incidence was considered 3%. All positive patients had mild or asymptomatic COVID-19. None of the patients exhibited moderate or severe symptoms. In conclusion, this study revealed that the incidence of COVID-19 was low, and mild or subclinical infection was common even in patients with NMD and IEM, who may be at a higher risk of severe COVID-19.