Background: One of the most important factors in the pathogenesis of COPD (chronic obstructive pulmonary disease) is oxidative stress. GGT (gamma-glutamyltransferase) has been regarded as a novel marker of oxidative stress over the last few years. This study aimed to compare the serum levels of GGT during stable and acute exacerbations of COPD at a single center. Material/Methods: The research included 117 patients with AECOPD (acute exacerbation of chronic obstructive pulmonary disease), 107 patients with stable COPD, and 112 control subjects. Serum GGT, spirometry function, and other clinical parameters (anthropometric and biochemical measurements) were evaluated and compared among the subjects. Results: Serum GGT was elevated in patients with stable COPD in comparison to the control subjects. Its level was inversely related to lung function. It was also significantly higher in AECOPD patients compared to stable COPD patients. We also found that a GGT level of 21.2 IU/L displays a reliable diagnostic prediction of COPD and that a GGT level of 26.5 IU/L can be applied to predict the exacerbation of COPD. Conclusions: Our research demonstrates that serum GGT level is inversely associated with pulmonary function and may serve as a biomarker during the progression of COPD. The monitoring of GGT values can be applied to evaluating COPD and its exacerbation risk.