Introduction: Self-poisoning is the most common form of hospitalised self-harm in young people and has been increasing over the last decade. The COVID-19 pandemic was associated with further increases in self-harm in adolescents. There are limited data on changes after pandemic restrictions ended. This study aimed to describe recent trends in self-poisoning in young people. Setting: Australia 2018–2023. Methods: A retrospective analysis of self-poisoning calls to Australia’s poisons information centres. Intentional poisoning exposures in people aged 5–19 years were included in the main analysis. We also examined intentional poisonings in people aged 20 and over for comparison. We used interrupted time-series analysis to estimate the impact of COVID-19 (March 2020) and ‘re-opening’ (December 2021), when many restrictions were lifted in Australia. We compared effects in the jurisdictions with most disruptions and lockdowns with other jurisdictions. Results: There were 201,755 self-poisonings documented, 64% female, with 19,946 children (aged 5–14, 9.9%) and 44,388 adolescents (aged 15–19, 22.0%). There was a steep increase in the rate of poisoning in female children and adolescents – with the annual increase being 1.361 (95% confidence interval = [1.074, 1.735]) and 1.154 (95% confidence interval = [1.049, 1.283]) times faster than pre-pandemic trends in these two groups between March 2020 and December 2021. Following relaxation of restrictions, there was a sudden drop and then slow decline in self-poisonings (despite rising COVID-19 infection rates). There was an overall 29.6% increase in intentional poisonings in young people over the study period. This is markedly more pronounced among young females (37.0%) vs males (11.2%). There were substantial jurisdictional variations, with larger increases in Victoria, Tasmania and the Australian Capital Territory. Conclusion: There has been a marked increase in child and adolescent female self-poisonings over the last 6 years, with increases strongly associated with COVID-19 pandemic restrictions but persisting after their removal.