Background: Organophosphorus (OP) compounds are commonly used pesticides. In OP poisoning, intermediate syndrome (IMS) manifests between the end of the acute cholinergic crisis and delayed neuropathy. Respiratory paralysis in IMS, if identified early can reduce the need for ventilator support, morbidity, and mortality. Serum creatine phosphokinase (CPK) is elevated in IMS. The objectives of our study were to measure serum CPK level, correlate CPK levels with severity of poisoning and estimate atropine dose used. Materials and Methods: A prospective, observational study was conducted for 1-year. Patients diagnosed with OP poisoning were included. Demographic characteristics, type of poison, time since poisoning, Peradeniya Organophosphorus Poisoning (POP) score, serum pseudocholinesterase, CPK levels, atropine dose, and outcome of treatment were documented. Results: Seventy-five patients were recruited of which 57% and 43% were males and females, respectively, with a mean age of 31.48 ± 11.76 years. The most common OP compound was chlorpyriphos followed by triazophos and methylparathion. The time required to reach hospital was 181.26 ± 89.53 min. About 73.3% and 26.7% of patients had mild and moderate poisoning, respectively, as per POP scale. Pseudocholinesterase level was 364 (205-2168) IU. The amount of atropine used was 190.66 ± 78.83 mg. Serial serum CPK values were 279.72 ± 350.21 IU, 389.78 ± 376.33 IU and 163.13 ± 155.15 IU at admission, 48 h, and 96 h after admission, respectively. A weak positive correlation between serum CPK levels and severity of poisoning (r = 0.352) was observed. All patients recovered completely within 10.69 ± 5.57 days. Three patients developed IMS, and their serial CPK levels were 1837.33 ± 243.19 IU/L, 1935 ± 97.41 IU/L, and 714.66 ± 394.82 IU/L; and recovered in 17 ± 5.6 days. Conclusion: Increased serum CPK levels at 48 h after poisoning was observed in all the patients, but three patients had more than 1500 IU/L, who manifested with IMS. Early diagnosis of IMS by serial estimation of CPK may help in timely intervention and reduce further life-threatening complications.