Objectives: The consequences of antibiotics-associated non-nutritional hypernatraemia may have a positive clinical impact on the mitigation of the COVID-19 related hyponatremia complications. This study aimed to explore the positive utility of Piperacillin/Tazobactam-associated sodium loading in COVID-19 patients. Methods: A retrospective study was conducted between Mar 2020 and Sep 2021. Eligible patients were stratified into two antibiotics-based cohorts; Non-Tazocin Cohort and Tazocin Cohort. One-Sample and Independent T-Tests and Chi-Square Test were conducted and the corrected sodium and its changes from baseline were run into the Receiver Operating Characteristics Tests followed by Sensitivity analysis. Results: The incidence of hyponatremia was significantly higher in Cohort I compared to Cohort II [378 (100.0%) vs 248 (61.5%), respectively, p-value=0.00]. The corrected sodium concentration was significantly lower in Cohort I compared to Cohort II [134.85±4.59 mEq/l vs 137.19±4.93 mEq/l, -2.34±0.34 mEq/l, p-value=0.00]. The mortality risk estimate for our institutional COVID-19 on PIP/TAZ vs Non-PIP/TAZ was 0.98 (95% CI; 0.74-1.29). 1.215 (95% CI; 0.85-1.73). Conclusion: Piperacillin/Tazobactam antibiotics administration in SARS-CoV-2 infected patients may have a non-antibiotic mortality benefit via its clinically significant propensity to mitigate the risk of hyponatremia-related negative clinical consequences, including mortality. This study investigated that it was optimally to keep averaged sodium concentrations above 133.85 mEq/l and to restrict dropping in sodium concentration by more than 1.95% from baseline.