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Background: Alcohol withdrawal syndrome is a potentially life-threatening condition with severe complications such as withdrawal seizures and delirium tremens. A valid and reliable biomarker for predicting the severity of alcohol withdrawal can be instrumental in individualizing effective therapy at the earliest. Methodology: This was an observational study done on 120 patients to study the relationship between serum creatine phosphokinase (CPK) levels with severity of alcohol withdrawal. The assessment for the severity of alcohol withdrawal was done with Clinical Institute Withdrawal Assessment for Alcohol-revised (CIWA-Ar) scale and an association was studied between the serum CPK levels and the severity of alcohol withdrawal. The data was analyzed using Chi-square test and Kruskal–Wallis tests. Results: The severity of alcohol withdrawal as per the CIWA was 26.66% mild, 55% moderate, and 18.33% severe. The mean serum CPK level for mild withdrawal was 126.93 IU/L, moderate withdrawal was 303.66 IU/L, and for severe withdrawal was 780.81 IU/L. A statistically significant association was obtained indicating that patients with higher CIWA-Ar scores are likely to have a higher level of serum CPK levels. Conclusion: Serum CPK levels were significantly associated with severity of alcohol withdrawal and can possibly serve as a candidate biomarker.