Background: Feline calicivirus (FCV) is a common pathogen causing widely prevalent upper respiratory disease for kitten and felines in recent years. Due to the substantial genetic variability of the viral genes, existing vaccines cannot provide complete protection. Therefore, researches on FCV antiviral drugs have received much attention. Results: In this study, we found that copper chloride had dose-dependent antiviral effects against FCV in F81 cells. We also found that the combination of copper chloride and ribavirin had a synergistic effect against FCV in the F81 cells. In contrast, the combination of and horse anti-FCV immunoglobulin F(ab’) 2 showed an antagonistic effect, likely because the copper chloride has an effect on the F(ab’) 2 immunoglobulin; however, further research is needed to clarify this supposition. Conclusions: In summary, we found that copper chloride had low cytotoxicity and significant antiviral effects against FCV in F81 cells, providing a new drug candidate for the prevention and treatment of FCV infection.