Background: Human serum paraoxonase-1 (PON-1) hydrolyzes organophosphate compounds (OPC) and so significantly alters an individual’s susceptibility to the toxicity of these chemicals. Aim: The study was designed to assess the serum PON-1 activity in patients with OPC poisoning and to correlate its level with the severity and outcome of acutely organophosphate poisoned patients. Patients and methods: This was a prospective clinical study that was performed at Benha Poison Treatment and Toxicological Research Unit (BPTTRU), Benha University Hospitals, Egypt, for one year, from 1 August 2020 till 31 July 2021. Patients were divided into case and control groups. Socio-demographic information of patients, clinical findings, treatments given, length of hospital stay and outcome were collected into datasheets. Patients were classified according to degree of toxicity according to Peradeniya Organophosphorus Poisoning (POP) scale. Blood samples were collected from patients to assess pseudocholiesterase and PON-1 activities. Results: Reduction of serum pseudocholinesterase and paraoxonase-1 (PON-1) activities in poisoned patients and patients can be graded according to (POP) scale into: mild, moderate and severe cases. In conclusion: This study concluded that serum paraoxonase-1 (PON-1) activity was significantly lower in patients with severe organophosphorus compounds (OPC) poisoning as compared to patients with moderate poisoning. Lower PON-1 activity was significantly associated with lower serum cholinesterase and poorer outcomes. PON-1 activity may be considered as an indicator of prognosis in OPC poisoning