Objective: To evaluate the feasibility of using serum globulin electrophoresis as a marker of the prognosis of acute exacerbation of chronic obstructive pulmonary disease (COPD) initiated by infection. Methods: One hundred and twenty patients with acute exacerbation of COPD from January 2015 to January 2017 in Wuhan Jinyintan Hospital were retrospectively collected. The patients was divided into a high concentration group (≥6.6 g/dL) and a low concentration group (<6.6 g/dL) according to the level of gamma globulin. The general features, pre-study state, pre-admission treatment, GOLD grade, BODE index, the cause of acute exacerbation, complication, FEV1/FVC, FEV1, and FVC were compared between these two groups. The correlation between Gamma globulin concentration and GOLD grade, other prognostic factor, early progress of acute exacerbation of COPD and 1-year overall survival rate were analyzed and compared. Results: There was no significantly difference between the two groups of correspondent general features, pre study state, and the cause of acute exacerbation. The percentage of pulmonary heart disease of the low concentration group was significantly higher than that in the high concentration group (23.3% vs 5.6%, P=0.011). The FEV1, FEV1/FVC and FVC of low concentration group was significantly lower than that in the high concentration group (P<0.05). The level of gamma globulin of mild COPD was significantly higher than that in the middle, severe, and extreme severe COPD [(13.4±2.09) g/dL vs (8.7±2.23) g/dL vs (8.5±1.89) g/dL vs (6.77±1.93) g/dL, P<0.001]. The level of gamma globulin of patients received glucocorticoid was significantly lower than patients without glucocorticoid [(7.06±2.47) g/dL vs (8.98± 3.03) g/dL, P=0.001]. The level of gamma globulin of patients received home oxygen therapy was significantly lower that patients without oxygen therapy [(7.12±2.27) g/dL vs (8.64±8.11) g/dL, P=0.024]. The negative correlation was founded between the level of gamma globulin and PaCO2 (r=−0.161, P=0.085) and readmission times within 1 year after discharge (r=−0.263, P=0.005), while positive correlation was founded between the level of gamma globulin and FEV1/FVC (r=0.213, P=0.020) and FEV1 (r=0.244, P=0.007). The 1-year overall survival rate of low concentration group was 89.3%, which was significantly lower that 94.6% in the high concentration group (P=0.0037). Conclusion: The serum concentration of gamma globulin has a good correlation with FEV1 in acute exacerbation of COPD. The severity of COPD is associated with this simple biomarker, which may help identify high-risk patients with acute exacerbation of COPD.