Background: The objective of the study was to determine the prevalence of hyponatremia (HN) and its associated morbimortality in hospitalized patients receiving parenteral nutrition (PN). Methods: A retrospective study including 222 patients receiving total PN (parenteral nutrition group [PNG]) over a 7-month period in a tertiary hospital and 176 matched to 179 control subjects without PN (control subjects group [CSG]). Demographicdata, Charlson Comorbidity Index (CCI), date of HN detection-(serum sodium or SNa <135 mmol/L)-intrahospital mortality, and hospital length-of-stay (LOS) were registered. In the PNG, body mass index (BMI) and SNa before, during, and after PN were recorded. Results: HN was more prevalent in the PNG: 52.8 vs. 35.8% (p = 0.001), and independent of age, gender, or CCI (OR 1.8 [95% CI 1.1-2.8], p = 0.006). In patients on PN, sustained HN (75% of all intraindividual SNa <135 mmol/L) was associated with a higher mortality rate independent of age, gender, CCI, or BMI (OR 7.38 [95% CI 1.07-50.8], p = 0.042). The absence of HN in PN patients was associated with a shorter hospital LOS (<30 days) and was independent of other comorbidities (OR 3.89 [95% CI 2.11-7.18], p = 0.001). Conclusions: HN is more prevalent in patients on PN. Sustained HN is associated with a higher intrahospital mortality rate. Absence of HN is associated with a shorter hospital LOS.