The aim of the present systematic review was to assess and provide an up-to-date analysis of the impact of coronavirus disease 2019 (COVID-19) pandemic on the health-related quality of life (HRQoL) of children and adolescents. Thus, an electronic search of the literature, in two well-known databases (PubMed and Web of Science), was performed until February 2021 (without date restriction). PRISMA guideline methodology was employed and data regarding the HRQoL were extracted from eligible studies. Articles were included if they met the following inclusion criteria: (a) children and/or adolescent population (4 to 19 years old); (b) HRQoL as a main assessment; (c) German, Spanish, Portuguese, French, and English language; and (d) pre-pandemic and during pandemic HRQoL data. Following the initial search, 241 possible related articles were identified. A total of 79 articles were identified as duplicates. Moreover, 129 articles were removed after reading the title and abstract. Of the remaining 33 articles, 27 were removed since they were not focused on children or adolescents (n = 19), articles did not report pre- and post- pandemic HRQoL values (n = 6), articles were not focused on HRQoL (n = 6), and one article was an editorial. Finally, six studies fulfilled the inclusion criteria and, therefore, were included in the systematic review. A total of 3177 children and/or adolescents during COVID-19 were included in this systematic review. Three articles showed that COVID-19 pandemic significantly impacted the HRQoL of children and adolescents, and another did not report comparison between pre- and during COVID-19 pandemic, although a reduction in the HRQoL can be observed. Nevertheless, two articles did not find significant changes and another one did not report p-values. Regarding sex differences, only two studies analyzed this topic, observing no differences between girls and boys in the impact of COVID-19 pandemic on HRQoL. Taking into account these results, this systematic review might confirm that COVID-19 has a negative impact on the HRQoL of children and/or adolescents.