Background: The issue of organophosphorus (OP) poisoning remains a significant global health concern, especially prevalent in developing nations. In OP poisoning, elevated levels of Sr. CPK (creatine phosphokinase) are often observed due to rhabdomyolysis. This elevation can serve as an effective and cost-efficient marker to evaluate poisoning severity. Aims and Objective: This current investigation endeavors to assess serum creatine phosphokinase (CPK) level in OP poisoning and to find out its correlation with the severity of OP poisoning Methodology: A retrospective and prospective study spanning a duration of one and half year was carried out on patients with OP poisoning at a tertiary-level medical college. Results: Throughout the study duration, a total of 40 patients presented themselves. Instances of intentional self-poisoning (95%) outweighed those of accidental exposure (5%). The preponderance of patients were identified as housewives (32.5%), succeeded by individuals in occupations such as private job, farmers, studentship, sweepers and some were unemployed (5%). Among the toxins ingested by patients, Dichlorvas (42.5%) emerged as the predominant choice (35.74%). The mean duration of hospital stays varied among the different severity level. In terms of outcomes, 75% of patients survived without the need for mechanical ventilation and the mortality rate documented in our study stood at 10%. Mean CPK levels were 143, 497.25, and 1806.80 IU/L for mild, moderate, and severe cases of poisoning. Our study showed a significant positive correlation between serum CPK levels and the severity of acute OP poisoning, as determined by the PERADENIYA ORGANOPHOSPHORUS POISONING (POP) score. We observed a negative correlation between serum CPK and serum pseudocholinesterase levels. Furthermore, our study revealed that high CPK is associated with severe poisoning and mortality. Conclusion: Serum CPK level can be used as an alternative, equally effective and cost-efficient biomarker for assessing the severity of acute OP poisoning. However, the main disadvantage with this marker is its non-specificity.