Introduction Chronic obstructive pulmonary disease (COPD) is a cover term that includes a variety of progressively debilitating lung diseases. COPD includes both emphysema and chronic bronchitis. Although COPD is mainly a chronic disease, a substantial number of patients experience exacerbations that are related to a significantly worse survival outcome, especially with abnormal serum electrolyte level. Aim To detect the serum electrolytes disturbances in patients with acute exacerbation of COPD. Patients and methods A prospective study was conducted at Chest Department, El-Hussein University Hospital, Al Azhar University, on patients with acute exacerbation of COPD. The study was approved by the hospital ethics committee, and a written consent was obtained from each patient before the procedure. Results We found a significantly low level of serum sodium (Na) (131±4.45 mEq/l), potassium (3.19±0.96 mEq/l), magnesium (1.85±0.17 mEq/l), and chloride (84.75±7.31 mEq/l) in patients with acute exacerbation of COPD than their healthy controls (Na+=138±2.28 mEq/l, potassium=4.50±0.02 mEq/l, magnesium=2.20±0.14 mEq/l and chloride=100.30±2.67 mEq/l) (P<0.05). Conclusion In patients with acute exacerbation of COPD, there are abnormal serum electrolytes like sodium, potassium, magnesium, and chloride levels.