Preoperative patient optimization is increasingly recognized as key to good surgical outcomes. Preoperative hyponatremia is a modifiable risk factor linked to poorer postoperative outcomes in other surgical fields. We provide the first investigation of the association of preoperative hyponatremia with morbidity and mortality in patients undergoing cervical spine surgery. We queried the National Surgical Quality Improvement Program registry for patients who underwent cervical spine fusion. Preoperative serum sodium levels were classified as normal (135–145 mEq/L) or hyponatremic (<135 mEq/L); hypernatremic patients were excluded from the analysis. Multivariable logistic analyses using a multiple imputations methodology were performed to determine significant predictors of major morbidity and mortality (MMM). We included 20,817 patients, of whom 5.2% were hyponatremic at presentation. Preoperative hyponatremia was a significant predictor of MMM (odds ratio OR, 1.23; 95% confidence interval CI, 1.09–1.39), mortality (OR, 1.36; 95% CI, 1.03–1.77), major morbidity (OR, 1.24; 95% CI, 1.10–1.40), and odds of prolonged hospitalization (OR, 1.13; 95% CI, 1.04–1.23). Other significant predictors of MMM included age, undergoing an emergent versus nonemergent operation, having chronic obstructive pulmonary disease, having disseminated malignancy, being functionally dependent, presenting with sepsis or septic shock, and having an American Society of Anesthesiologists status of 3, 4, or 5. Similar results were seen in analyses using only complete cases and in sensitivity analyses. Using the National Surgical Quality Improvement Program database, hyponatremia is observed in approximately 1 in every 20 patients undergoing cervical spine fusion. More importantly, it is a predictor of mortality, major morbidity, and prolonged hospitalization. From a systems-level perspective, preoperative hyponatremia may therefore represent a point of intervention for preoperative patient optimization.