Background This study aims to evaluate the mental health status of children, adolescents and their parents during the first year of COVID-19 pandemic in Belgium. Method Analysis compared results before and during the second national lockdown, which started on November 2nd 2020. A cross-sectional online survey was conducted between May 2020 and April 2021. Results Two hundred and eighteen adults and 273 children fully completed the survey. Almost one in five children (17.9%) presented moderate-to-severe scores of depression. Adolescents presented a higher level of depression than children (p = 0.007). The rate of moderate-to-severe depression scores (10.8% to 21%, p = 0.007) and internalized symptoms increased during the second lockdown (p < 0.001). Parents' depression (p < 0.001) and anxiety (p = 0.027) levels also increased during the second lockdown. Logistic regression showed that the use of psychotropic medication in parents and parents’ depression scores were risk factors for children to have worse depression scores. Conclusion The second lockdown appears to worsen the effects of the pandemic on children’s and parents’ mental health. There is a need to implement specific interventions targeting both children/adolescents and their parents to support them during lockdown periods and improve mental health outcomes.