SARS-CoV-2 can remain viable on the protective face masks surface for several days. Mask touching, reuse and disposal occurs frequently, leading to increased risk of cross-contamination, infection and further transmission. Cuprous-oxide has potent virucidal properties. We determined the capacity of surgical face masks (type IIR) made with nonwoven fabric impregnated with cuprous-oxide microparticles (Test Fabric), to inactivate SARS-CoV-2 when in direct contact with the virus. The Test Fabric reduced the infectious titers of SARS-CoV-2 by 0.73, 3.02 and 4.19 log10 within 5, 30 and 60 minutes, respectively. In contrast, the infectious titers of the virus were reduced by Control Fabric by 0.24, 0.67 and 0.97 within 5, 30 and 60 minutes, respectively. The reductions were significantly higher in the Test Fabric than in the Control Fabric (0.49, 2.35 and 3.22 log difference, accordingly), reaching a statistically significant difference after 5 minutes (p < 0.01). The mask filtration properties were not affected by the presence of the cuprous oxide microparticles. We conclude that the use of cuprous-oxide containing face masks in the external layers of respiratory face masks may significantly reduce the risk of SARS-CoV-2 cross-contamination, transmission and infection, due to masks handling and disposal, especially when used by the general population.