Background: Unintentional poisoning by substances of abuse in children is a rare type of acute poisoning but recently, it has been increased in many countries. Low dose of these substances can be fatal for children under 6 years old resulting in severe morbidity and mortality if it is not timely diagnosed and properly managed. Aim :this study was aimed to describe the pattern of unintentional poisoning by substances of abuse among children below 6 years old who were presented to the Poison Control Center of Ain Shams University Hospitals (PCC-ASUH), Egypt during a 4 -year period (2014-2017). Material and methods: A retrospective study was performed on all infants and children aged less than 6 years old with unintentional poisoning by substances of abuse presented to the PCC-ASUH during the four years period (2014-2017). The data were collected and included: demographic, poisoning and clinical data. Treatment given to the patients, length of hospital stays as well as outcome of patients were also recorded. Results: During the studied period (2014- 2017), there were 436 children below 6 years old with unintentional poisoning by substances of abuse. Children from 1 to 2 years old were the most vulnerable age group to unintentional poisoning with substances of abuse (64%), the majority were males (58%), most of them were from Cairo (61%). The most common substance of abuse unintentionally ingested among studied children was cannabis (64%), followed by tramadol (33.5%) and opium (2.5%). Loss of consciousness was the most common recorded symptom among children (80%). Most of the patients were admitted to the inpatient unit (60%) while 30% of cases were admitted to the Intensive Care Unit (ICU). There were 9 deaths (2%): eight children were intoxicated with tramadol and one child with opium poisoning. Conclusion: This study concluded that unintentional poisoning by substances of abuse in children is a life threatening condition and clinicians should consider it if any child presented to the ER with sudden onset of coma without any history of fever or primary illness. The most frequent unintentionally ingested substance of abuse among children was cannabis followed by tramadol.