This study sought to elucidate the relationship between the variability of serum potassium ion levels and the 28-day mortality rate in patients admitted to the Intensive Care Unit (ICU). Incorporating a cohort of 237 patients from the First Affiliated Hospital of Guangxi Medical University (October 2022 to October 2023), the investigation utilized the coefficient of variation to assess serum potassium ion variability. Employing binary logistic regression analysis and adjusting for potential confounding factors, the study unveiled a significant positive correlation between the variability in potassium ion levels and the 28-day mortality rate. Notably, the deceased patients demonstrated a mean increase of approximately 0.13 mmol/L in potassium levels every 12 hours, a contrast to the trends observed in survivors. This positive correlation persisted even after excluding patients who experienced hypokalemia or hyperkalemia during their hospitalization. The study thus underscores the significance of potassium ion variability as a prognostic indicator of 28-day mortality, irrespective of the patients maintaining normal potassium ion concentrations.