Francisellosis is a disease responsible for severe economic losses in aquaculture. Currently, this disease is controlled via biosecurity measures and treatment of affected batches. In this study, tilapia juveniles were challenged with Francisella orientalis via immersion and fed with oxytetracycline‐medicated feed, at 100 mg kg fish−1 and 200 mg kg fish−1, under prophylactic and therapeutic strategies for 16 and 15 days respectively. All doses and treatment strategies reduced the fish mortality. The detection of the pathogen from the spleen was lower in the treated groups. Histopathology analysis showed that challenged fish that received the highest dosage presented fewer granuloma in their spleens and less inflammatory infiltrate in their livers than untreated fish. Fish that received the prophylactic treatment, regardless of the dose, presented fewer granuloma in their livers than untreated fish. Fish treated with 100 mg kg fish−1 had better scores for hepatocyte accumulations than fish treated with the higher dosage. Furthermore, 20% of the unchallenged fish that received the higher dosage presented mild inflammatory infiltrate in their livers. No differences were observed in the serum hepatocyte lesion enzyme quantifications. The results indicate that oxytetracycline‐medicated feed is safe, even at the higher dose, and effective at controlling francisellosis in tilapia.