PURPOSE: The COVID-19 pandemic has been associated with a decline in mental health of adolescents. The aim of this study was to analyze the rate of deliberate self-poisonings (DSPs) among adolescents reported to the Dutch Poisons Information Center before and during the COVID-19 pandemic. METHODS: A retrospective study from 2016 until 2021 was performed to characterize DSPs among adolescents, and to analyze trends in the number of DSPs. All DSPs among adolescents with the age of 13 up to and including 17 years were included. DSP characteristics included: age, gender, bodyweight, used substance, dose, and treatment advice. Trends in the number of DSPs were analyzed using time series decomposition and Seasonal Autoregressive Integrated Moving Average models. RESULTS: Six thousand nine hundred fifteen DSPs in adolescents were recorded from January first 2016 until December 31st 2021. Females were involved in 84% of adolescent DSPs. A strong increase in the number of DSPs was observed in 2021 (45% increase compared to 2020), which deviated from the predicted trend based on previous years. This increase was most prominent in 13-, 14-, and 15-year-old female adolescents. Commonly involved drugs were paracetamol, ibuprofen, methylphenidate, fluoxetine, and quetiapine. The contribution of paracetamol rose from 33% in 2019 to 40% in 2021. DISCUSSION: The strong increase in the number of DSPs during the second year of the COVID-19 pandemic suggests that long-term containment measures such as quarantines, lockdowns, and school closures may enhance self-harm behavior among adolescents, especially among younger females (13-15 years of age), with a preference for paracetamol as DSP substance