Background: Substances use poisoning is considered a great social dilemma. The attention to this dilemma has increased in response to the stress and isolation occurred as consequences to COVID19 pandemic lockdown. Aim of the work: The aim of this work was to evaluate the impact of lockdown due to COVID-19 on the pattern of acute intoxication by substances of abuse in Tanta University Poison Control Center (TUPCC), Egypt. Patients and Methods: Substance abusers' patients with acute intoxication who were admitted to Tanta University Poison Control Centre (TUPCC) in Egypt were the subjects of this cross-sectional comparative study. The study was carried out over two years. The first year was prior to the COVID-19 lockdown, which lasted from early March 2019 to late February 2020 (group 1). The second year was the year following Egypt's COVID-19 lockdown, which lasted from early March 2020 to late February 2021 (group 2). Results: The overall number of admitted patients decreased (from 112 to 72). There was significant increase in proportion of urban poisoned patient after the pandemic declaration (from 25% to 55.6%, P <0.001). Significant increase in time delay from (3.0±3.13) before the pandemic declaration to (9.1±16.25) (P<0.001) after the pandemic declaration. The need for ICU admission increased after the pandemic declaration from 7 cases to 14 cases (P=0.006). The mortality rate statistically increased after the declaration of pandemic from 5 patients to 11 patients (P=0.011). Sedative and hypnotics were the most prevalent poisons used by the patients in both years, with a statistical significant decrease after pandemic declaration (from 49.1% to 31.9%, P=0.021). Conclusion: Sedative and hypnotics were the most commonly used poison in the year after the pandemic was declared. This year also had high rates of ICU admissions and deaths, as well as significant delays in getting to the hospital.