Transporters in the human liver play a major role in the metabolism of endo-and xenobiotics. Apical (canalicular) transporters extrude compounds to the bile, while basolateral hepatocyte transporters promote the uptake or expel various compounds into the venous blood stream. In the present work we have examined the in vitro interactions of some key repurposed drugs advocated to treat COVID-19 (lopinavir, ritonavir, ivermectin, remdesivir and favipiravir), with the relevant key transporters in the hepatocytes. These transporters included the ABCB11/BSEP, ABCC2/MRP2, and MATE1 in the canalicular membrane, as well as ABCC3/MRP3, ABCC4/MRP4, OCT1, OATP1B1, OATP1B3, and NTCP, residing in the basolateral membrane. Lopinavir and ritonavir in low micromolar concentrations inhibited the ABCB11/BSEP and MATE1 exporters, as well as the OATP1B1/1B3 uptake transporters. Ritonavir had a similar inhibitory pattern, also inhibiting OCT1. Remdesivir strongly inhibited ABCC4/MRP4, OATP1B1/1B3, MATE1 and OCT1. Thus, these agents may cause severe drug-drug interactions and drug-induced liver injury. Favipiravir had no significant effect on any of these transporters. Since both general drug metabolism and drug-induced liver toxicity are strongly dependent on the functioning of these transporters, the variable interactions reported here may have important clinical relevance in the drug treatment of this viral disease and the existing co-morbidities.