Background: Muscle atrophy is a major clinical feature of chronic obstructive pulmonary disease (COPD), and it is considered a strong predictor of mortality in COPD patients. This study aimed to assess the use of serum creatinine/serum Cystatin C ratio in the assessment of muscle wasting and disease severity in stable COPD patients. Methods: This case-control study included 70 COPD patients and 20 age and gender-matched healthy controls. Pulmonary function tests, measurement of the serum creatinine (Cr) and cystatin C (Cys-C) levels, chest high-resolution CT images (HRCT) for the assessment of low attenuation area percentage (LAA%) and Erector Spinae muscle (ESM) thickness, routine laboratory investigations and arterial blood gases (ABG). Results: There was a significant positive correlation between serum cystatin c and severity of COPD and LAA% but there was a significant negative correlation between serum cystatin c and Erector Spinae muscle cross-sectional area (ESMCSA), forced vital capacity %predicted (FVC% predicted), forced expiratory volume in 1 second (FEV1%predicted) FEV1/FVC%, and body mass index (BMI). Moreover, there was a significant positive correlation between creatinine/ cysC ratio and BMI, ESMCSA, FVC% predicted, FEV1/ FVC % and FEV1% predicted. The cut-off points of ESMCSA and Cr/Cys C for severe COPD were 23.4 cm2 and 0.87 respectively. Conclusion: The present study indicated that the Cr/Cys C ratio is an easy, inexpensive, repeatable, and promising tool that allows us to evaluate muscle wasting in COPD patients using serum markers as there is a positive correlation between the degree of muscle wasting and the severity of COPD.