BACKGROUND Organophosphorus poisoning is possibly the most common acute poisoning in the developing countries and is a global health problem.1,2 Between 750,000 and 3,000,000 of OP poisoning occur globally every year.3 OP insecticides bind and irreversibly inhibit butyrylcholinesterase. These compounds cause excessive stimulation of muscarinic and nicotinic cholinergic receptors in the central and autonomic nervous systems and at skeletal neuromuscular junctions.4 Butyrylcholinesterase (BChE) is also known as pseudocholinesterase.5 Due to the limitations in accuracy and cost of plasma pseudocholinesterase level estimation, alternate biochemical marker options for OP poisoning have been studied for evaluation of patients with OP poisoning. Increased creatine phosphokinase (CPK) levels are seen in OP poisoning in early phase.6,7 This study was conducted to correlate initial serum CPK levels with the clinical severity at presentation and the final clinical outcome. METHODS This descriptive study was carried out after reviewing case records of patients >/= 18 years with acute organophosphorus (OP) poisoning who were admitted under the Internal medicine department of Government Medical College Thiruvananthapuram between January 2019 and December 2019. The severity of poisoning was categorized based on Peradeniya organophosphorus poisoning (POP) scale. Serum CPK level, serum pseudocholinesterase, and total dose of atropine in milligrams until the outcome in the hospital were recorded. The student's t-test and Pearson's correlation coefficient were used for the assessment of statistical significance. RESULTS Clinical severity as per POP SCALE was mild (score 0–3) in 24 (27 %), moderate (score 4–7) in 50 (55.81 %) and severe (score 8–11) in 16 (18 %) patients. Serum CPK, serum pseudocholinesterase level, and total atropine dose strongly correlated with clinical severity of OP poisoning. Our study strongly recommends serum CPK as an alternative marker. CONCLUSIONS Serum CPK level can be an effective biomarker in acute OP poisoning because its level can predict the prognosis of OP poisoning. KEY WORDS Creatine Phosphokinase, Organophosphorus Poisoning, Severity.