PurposeMaintaining the proper fluid balance is a fundamental step in the management of hospitalized patients. The current study evaluated the impact of negative fluid balance on outcomes of patients with confirmed COVID-19.MethodsWe considered the negative fluid balance as a higher output fluid compared to the input fluid. The fluid balance was categorized into four groups (group 4: −850 to −500 ml/day; group 3: −499 to −200 ml/day, group 2: −199 to 0 ml/day, and group 1 : 1 to 1000 ml/day) and included ordinally in the model. The outcomes were all-cause mortality, length of hospitalization, and improvement in oxygen saturation.ResultsThe fluid balance differed significantly among nonsurvivors and survivors (MD: −317.93, 95% CI: −410.21, −225.69, andp< 0.001). After adjusting for potential confounders, there was a significantly lower frequency of mortality in patients with negative fluid balance compared to the controls (aRR: 0.69, 95% CI: 0.57, 0.84, andp< 0.001). Similarly, the length of hospitalization was significantly shorter in the negative fluid balance group in comparison to the control group (aMD: −1.01, 95% CI: −1.74, −0.28, andp=0.006).ConclusionWe determined that the negative fluid balance was associated with favorable outcomes in COVID-19 patients. The negative fluid balance was associated with the reduced mortality rate and length of hospitalization as well as improvement in oxygen saturation. Moreover, the NT-proBNP >781 pg/mL and fluid balance >−430 mL might be the predictors for positive fluid balance and mortality, respectively.