Background/Objectives: Hyponatremia is defined as a serum sodium concentration below 135 mEq/L. It is associated with increased morbidity and mortality. This study aimed to determine the factors associated with mortality in patients hospitalized with moderate to severe hyponatremia in the nephrology clinic and nephrology intensive care unit during an eight-year follow-up period. Methods: This retrospective study included patients admitted between January 2018 and October 2025 who were hospitalized due to moderate or severe hyponatremia. Results: Of 4270 patients, 337 (7.8%) were hospitalized with moderate to severe hyponatremia. The majority of patients were female (60.2%; n = 203). 242 patients (71.8%) had severe hyponatremia. The most common presenting complaint was nausea and vomiting, the most common month and season of presentation was July-Summer, and the most common cause of hyponatremia was drug-induced hyponatremia. The mortality rate was 40.7% (n = 137). The most common cause of death was decompensated heart failure. Factors independently affecting mortality; age (HR = 1.018, 95% CI 1.001–1.037, p = 0.047), malignancy (HR = 2.397, 95% CI 1.459–3.939, p < 0.001), number of hospitalizations (HR = 0.377, 95% CI 0.228–0.623, p < 0.001), EF (HR = 0.972, 95% CI 0.956–0.988, p < 0.001), high phosphorus (HR = 2.397, 95% CI 1.527–3.764, p < 0.001), furosemide use (HR = 1.638, 95% CI 1.018–2.636, p = 0.042) and fluid restriction. Conclusions: Advanced age, malignancy, high phosphorus levels, furosemide use, and fluid restriction were associated with increased mortality, whereas higher ejection fraction and greater number of hospitalizations were protective. These findings emphasize the importance of individualized management strategies and close follow-up in patients with moderate to severe hyponatremia.