A key element to the prevention and management of the COVID-19 pandemic is the development of effective therapeutics. Drug combination strategies of repurposed drugs offer a number of advantages to monotherapies including the potential to achieve greater efficacy, the potential to increase the therapeutic index of drugs and the potential to reduce the emergence of drug resistance. Combination of agents with antiviral mechanisms of action with immune-modulatory or anti-inflammatory drug is also worthy of investigation. Here, we report on the in vitro synergistic interaction between two FDA approved drugs, remdesivir (RDV) and ivermectin (IVM) resulting in enhanced antiviral activity against SARS-CoV-2, the causative pathogen of COVID-19. These findings warrant further investigations into the clinical potential of this combination, together with studies to define the underlying mechanism.