Vaccines are an important part of the COVID-19 pandemic response plan. This cross-sectional study aims to assess the attitude and perception levels of parents toward COVID-19 vaccines for children aged 0–18 years in the Aseer region of Saudi Arabia. Data were analyzed using SPSS version 16.0. Out of a total of 1463 parents, 30.6% assumed that COVID-19 vaccination may be more dangerous for children than adults. Nearly 36.5% parents don’t have any concern about children’s vaccination. About 12.8% of children have not received the vaccination, 55% of parents have some sort of hesitation and 32.2% of parents did not hesitate before vaccinating their children against COVID-19. Only 15.4% of parents expect that the COVID-19 vaccine affects their child’s genes. About 23.4% parents strongly agreed and 35.1% agreed about the importance of getting their children vaccinated. About 22.1% of parents strongly agreed and 33.3% agreed regarding their willingness to get their children vaccinated to prevent Coronavirus disease. More than 80% of parents recommended rushing to receive the COVID-19 vaccine. Health professionals and policymakers should implement and support strategies to ensure children are vaccinated for COVID-19. They also need to educate parents and families regarding childhood vaccination.