Background: Acute exacerbations of Chronic Obstructive Pulmonary Disease (COPD) significantly contribute to patient morbidity and mortality. Although electrolyte imbalances may influence the course and severity of these exacerbations, they are not well characterized in clinical practice. Objectives: To assess the pattern and frequency of serum electrolyte abnormalities during acute exacerbations of COPD compared to the stable disease state, and to explore their association with clinical parameters and disease severity. Methods: A hospital-based study was conducted involving 120 COPD patients—60 experiencing acute exacerbations and 60 in a stable phase. Data collected included demographics, clinical features, pulmonary function tests, and serum sodium and potassium levels. In the exacerbation group, electrolytes were measured at both admission and discharge. Results: Patients with acute exacerbations were older (mean age: 65.62 vs. 63.15 years; p=0.038) and more likely to be current smokers (33.3% vs. 0%; p<0.001). Hyponatremia and hypokalemia were significantly more common in the exacerbation group (95.0% and 91.7%, respectively) compared to the stable group (both 0%; p<0.001). Mean serum sodium and potassium levels were substantially lower during exacerbation (128.95 mEq/L and 3.07 mEq/L) than in the stable phase (138.17 mEq/L and 4.01 mEq/L; p<0.001). Strong inverse correlations were found between electrolyte levels and MMRC dyspnea scores (sodium: r = –0.76; potassium: r = –0.70), GOLD stages (sodium: r = –0.85; potassium: r = –0.81), and respiratory rate, with positive correlations observed with oxygen saturation (p<0.001 for all). Conclusion: Electrolyte disturbances, particularly hyponatremia and hypokalemia, are highly prevalent during acute COPD exacerbations and show strong correlations with clinical markers of disease severity. Routine monitoring and timely correction of electrolyte imbalances should be integrated into the management of COPD exacerbations.