Nasal irrigation is thought to decrease the viral load present in the nasal cavity. Our aim was to assess the effect of a hypertonic seawater solution [with algal and herbal natural ingredients (Sinomarin®)] on the viral load of nasopharynx in patients hospitalized with severe COVID-19 pneumonia. We conducted a prospective, randomized, controlled trial from June 2022 to December 2022. We allocated 56 patients with COVID-19 pneumonia into two groups (28 in each group)—the hypertonic seawater group [nasal irrigations with a hypertonic seawater solution (Sinomarin®) every 4 h for 16 h per day, for two consecutive days] and the control group (no nasal irrigations). A second nasopharyngeal swab was collected 48 h after the baseline nasopharyngeal swab (8 h after the last wash in the hypertonic seawater group) to estimate the SARS-CoV-2 viral load as determined by cycle threshold (Ct) values. In the hypertonic seawater group, the mean Ct values significantly increased two days after the initial measurement [ΔCt 48−0 h = 3.86 ± 3.03 cycles, p < 0.001 (95%CI: 2.69 to 5.04)]. No significant differences in the Ct values were observed in the control group [ΔCt 48−0 h = −0.14 ± 4.29, p = 0.866 (95%CI: −1.80 to −1.52)]. At follow-up, 17 patients from the hypertonic seawater group had negative test results compared to only 9 patients from the control group (p = 0.03). Nasal irrigations with a hypertonic seawater solution containing algal and herbal natural ingredients significantly decreased nasopharyngeal viral load and the detection time of SARS-CoV-2 in the nasal cavity.