Background:Patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) had a prevalence of acute kidney injury (AKI) between 1.9% and 21.3%. It has been suggested that serum protein cystatin C (Cys C) can be used as a marker for the early detection of AKI. Objective: This study aimed to assess the role of cystatin C in prediction of acute kidney injury in patients with chronic obstructive pulmonary disease (COPD). Patients and methods: The study was conducted on 150 subjects divided into three groups: Group (1) included fifty patients with an AECOPD, group (2) included fifty patients with stable COPD without exacerbation and group (3) included fifty subjects as control subjects who were recruited from the general population and matched for age and sex. All participants were subjected to full history taking, clinical assessment and laboratory investigations. Serum creatinine at admission and after 48 hours was estimated. Pulmonary function test (PFT) was performed using a spirometry. Serum Cys C levels was measured for all subjects. Results: There was a high statistically significant (p-value < 0.001) increase of Cys C level in AECOPD group (median = 0.95, IQR = 0.86 – 1) when compared to stable COPD group (median = 0.7, IQR = 0.64 – 0.79) and control group (median = 0.6, IQR = 0.58– 0.61). Serum Cys C can be used to discriminate between AECOPD group and stable COPD group at a cutoff level of > 0.79, with 96% sensitivity, 88% specificity, 88.9% PPV and 95.7% NPV (AUC = 0.97 & p-value < 0.001). Conclusion: Patients with AECOPD who had serum cystatin C level more than 0.79 are thought to have a higher risk of developing HA-AKI. Serum Cystatin C level is negatively correlated with FEV1 and FEV1/FVC. We recommend using of serum Cystatin C for prediction of AKI in COPD patients.