© 2022Capripoxvirus diseases are listed as reportable diseases by World Organization for Animal Health (OIE). Lumpy skin disease virus (LSDV) and sheeppox virus (SPPV), which can only be distinguished by molecular analysis, cause moderately, severe, or sometimes fatal infections in cattle and sheep. Even though vaccines are the most effective way to control the infection, their effectiveness may decrease in some cases. Therefore, it is significant to explore antiviral drugs against these diseases along with the vaccine. This study aimed to investigate the antiviral efficiency of ivermectin (IVM) at different stages of in vitro replication of LSDV and SPPV. For this purpose, viral titers (TCID50/mL) of the viruses not treated with IVM (0.0 μM) and treated with non-cytotoxic concentrations of IVM (1.0 and 2.5 μM) were compared during a nine-day (216 h) post-infection period by viral titration assay. At 2.5 μM concentrations of IVM, the mean viral titer was significantly (P<0.05) reduced by approximately three logs for the replication stage of LSDV and SPPV. To evaluate the antiviral activity of IVM against LSDV and SPPV by treatment at the virus attachment and penetration stages, the titers of the virus either untreated or treated with 2,5 μM IVM were compared by virus titration assay. The number of infectious virions for LSDV and SPPV were decreased by 99.82% and 99.87% at the viral replication stage, 68.38% and 25.01% at the attachment stage, and 57.83% and 0.0% at the penetration stage, respectively. It was determined that ivermectin is statistically more effective on LSDV than SPPV at the virus attachment and penetration stages (P<0.05). This study found that the drug IVM can inhibit capripoxviruses, including LSDV and SPPV at various stages of the propagation. Moreover, this research predicted the in vitro antiviral ability of IVM against capripoxvirus infections for the first time.