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Background: In individuals with coronavirus disease (COVID-19), the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load (VL) plays an important role in infectivity., Objectives: This study aimed to evaluate the reduction in the VL and infectivity induced by phthalocyanine mouthwash and nasal spray in patients with COVID-19., Methods: Patients with mild COVID-19 were recruited to participate in a triple-blinded randomized controlled trial. Participants were assigned to one of three groups: Group 1, non-active mouthwash and saline nasal spray (SNS); Group 2, phthalocyanine mouthwash and SNS; and Group 3 phthalocyanine mouthwash and phthalocyanine nasal spray. VL was assessed in nasopharyngeal and oropharyngeal swabs collected at the time of clinical diagnosis at baseline as well as 24 and 72 hours after starting the rinsing protocols., Findings: Forty-six participants were included in the analysis: 15, 16, and 15 in Groups 1, 2, and 3, respectively. After 72 hours, the reduction in VL was significantly higher in Group 3 (mean cycle threshold (Ct) decrease: 11.21) than in Group 1 (mean Ct decrease: 5.53). Additionally, only the mean VL in Group 3 was reduced to a non-contagious level after 72 hours., Main Conclusions: Use of phthalocyanine mouthwash and nasal spray is effective at reducing SARS-CoV-2 infectivity., Competing Interests: Dr. Vilhena has a patent classification pending. Prof. Dr. da Silva Santos reports grants from CNPq process nº 309525/2018-7. The other authors declare that they have no competing interests., (Copyright © 2023 Colado Simão et al.)