Equine Piroplasmosis (EP) is a disease that negatively impacts the horse industry worldwide and is caused by two distinct species of protozoan parasites, Babesia caballi and Theileria equi. Currently the United States is considered free of EP and strict regulations are in place to prevent its introduction. If an outbreak does occur, there are two options for infected horses: lifelong quarantine or humane euthanization. Treatment options are limited in their ability to clear infection. Rifampicin and fosmidomycin are anti-microbial agents that are successful at treating related protozoan diseases, such as malaria. These two drugs were screened for anti-protozoal properties against the erythrocytic stage of T. equi and B. caballi by performing in vitro inhibition assays. Parasite growth was evaluated over a 72 h treatment period and was significantly reduced for both species with notable morphological changes. Rifampicin was shown to possess more potent effects at lower concentrations than fosmidomycin for both T. equi and B. caballi. Based on data acquired during the trial, further in vitro and in vivo tests should be performed for rifampicin and fosmidomycin. Further, the results attained suggest that other existing anti-microbials should be evaluated for their efficacy in treating EP