Importance: SARS coronavirus 2 (SARS-CoV-2) is spread mainly through airborne transmission and colonizes the human upper respiratory tract. It causes coronavirus disease 2019 (COVID-19), which has major therapeutic challenges as there are no treatments to prevent the infection from spreading or the development of the disease in a severe form. Objective: COVID-19 is diagnosed through identification of viral genetic material from nasopharyngeal swabs using PCR. The quantification of viral RNA using the cycle threshold (Ct) values is of great diagnostic importance. Nasal wash with saline or hypertonic saline is very important for the hygiene of the nose and sinuses. The aim of this research was to investigate the effect of an intense nasal wash on the viral load in patients with a SARS-CoV-2 infection. Design: A case-control study investigating the association of a nasopharyngeal wash and viral load in adult patients who tested positive for COVID-19 and were hospitalized was performed. All patients were treated with the standard protocol of care for COVID-19. Group A (n = 20) patients were each provided with a 25 mL bottle of hypertonic solution for a nasopharyngeal wash to be performed for 20–30 s, thrice within 6 h. Group B (n = 5) patients served as negative controls (no intervention). Nasal swabs were taken before and after the 6-h period by the same doctor and RT-PCR followed. Results: There was a 23.6% (median value) and 17.3% (mean value) reduction in the viral load after nasopharyngeal washing. On the other hand, Ct values remained practically stable for the negative control patients within the same 6-h period. Conclusion: To the best of our knowledge, this is the first study which demonstrates the potential effect of hypertonic water on the reduction of SARS-CoV-2 viral load in hospitalized patients with COVID-19. Further randomized, controlled studies are needed to confirm the effects of hypertonic water on the prevention and clinical outcome of SARS-CoV-2-infected patients.