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Background: The success of phage therapy is affected by the method of treatment delivery. This study focused on comparing different phage delivery routes, specifically oral (phage-impregnated feed), intraperitoneal (IP), and bath (immersion), in treatment of induced motile Aeromonas septicemia (MAS). Materials and Methods: The efficacy of Aeromonas hydrophila phage cocktail in treating MAS-infected Oreochromis niloticus through different delivery routes was assessed by challenging the fish with 100% lethal dose of A. hydrophila and conducting a 15-day treatment regimen. Blood and kidney samples were analyzed for bacterial and phage concentrations. Results: All routes exhibited reduction of disease symptoms, significant ( p  < 0.05) decrease in bacterial count, and increase in phage count. Notably, IP route showed significant activity in reducing bacterial load. Conclusions: Phage therapy through IP route is the most effective yet invasive in controlling MAS infection in O. niloticus . The efficacy of oral route depends on the fish's intake of feeds, whereas the bath route was the least effective., Competing Interests: No competing financial interests exist., (Copyright 2020, Mary Ann Liebert, Inc., publishers.)