Background: Acute organophosphorus poisoning (AOPP) is one of the important causes of morbidity and mortality especially in developing countries. Exposure to organophosphorus (OP) compounds leads to inhibition of cholinesterase enzyme, resulting in overstimulation of muscarinic and nicotinic receptors. Hence, central, peripheral and autonomic manifestations may lead to death. The lack of valid scoring systems for classification of AOPP severity, render difficult outcome prediction and inaccurate potential complication incidence. There are emerging options for new biochemical markers in AOPP that may facilitate the prediction of severity and/ or outcome. Aim of the work: Evaluation and correlation of the role of serum Copeptin level and Peradeniya organophosphorus poisoning (POP) scale in predicting AOPP severity and outcome in 90 AOPP patients admitted to the Poison Control Center - Ain Shams University Hospitals (PCC-ASUHs). Subjects and Methods: A prospective cross sectional, hospital-based study carried out on 90 AOPP patients admitted to PCC- ASUHs. The diagnosis was verified by history of OP exposure, initial assessment of clinical manifestations and serum Pseudocholinestrase level measurement. Results: In the current study, according to POP scale 48% of the patients were mild, 42% were moderate and 10% were severe cases. Deaths were reported among 11% of the cases. Serum Copeptin level was positively associated with the severity and outcome, with cut off level ≥ 3.9 ng/ml for mortality prediction. POP score was directly proportional with hospital stay duration, serum Copeptin level and the outcome. Hospital disposition, mechanical ventilation and coma were positively associated with the degree of severity. Conclusion: Our study concluded that POP scale can be used as a reliable scoring system for AOPP classification of severity and early detector of hospital disposition either ICU or in- patient, hospital stay duration, total atropine dose, incidence of mechanical ventilation and mortality. Serum Copeptin level is positively associated with AOPP severity and had a role in outcome prediction. Recommendation: Early assessment of AOPP severity by POP score can facilitate categorization of the patient's severity state and predict morbidity and mortality. Serum Copeptin level can be used as a tool for evaluation of severity and prognostic marker for the outcome of AOPP.