Coronavirus disease 2019 (COVID-19) pandemic spread rapidly and this scenario is concerning worldwide. In hospitalized patients, dysnatremia (hyponatremia and/or hypernatremia) is the most common electrolyte disturbance, being reported in 30–40% of cases and associated with a poor prognosis. This retrospective longitudinal study aimed to evaluate the association of dysnatremia with mortality in hospitalized patients infected with COVID-19. We analyzed data from hospital records of 1000 patients with COVID-19 (median age, 62.5 years; 57.1% men), including 109 (10.9%) deaths. Kaplan-Meier survival curves and Cox proportional hazard models with Hazard Ratio (HR) with 95% confidence intervals (95%CI) were applied to confirm the association between dysnatremia (hyponatremia and/or hypernatremia) and death. Hypernatremia was detected in 83 (76.1%) of the patients who died, with a cumulative reduction in survival (p < 0.01) and an increased risk for death by 2.4 fold (95%CI 1.4–2.9). In the multivariable analysis, hypernatremia was the main factor associated with increased mortality (HR:1.50; 95%CI:1.23–1.81). Other factors also associated with death were long length of stay (LOS) (HR:1.54; 95%CI:1.21–1.78), old age (HR:1.63; 95%CI:1.28–1.88), and kidney disease (HR:1.77; 95%CI:1.21–3.30). Hypernatremia during hospitalization is an important risk factor for poor prognosis and an increased risk (2.4) of mortality. LOS, old age, and kidney disease could also be used for risk stratification in patients with COVID-19.