Bacterial coldwater disease (BCWD), caused by Flavobacterium psychrophilum (Fp ), remains one of the most significant bacterial diseases of salmonids worldwide, and losses sustained in farmed salmonids are particularly substantial. Currently there are two antibiotics, Terramycin 200 (oxytetracycline dihydrate; OTC ) and Aquaflor (florfenicol; FFC) approved to treat Fp infections in food fish by the U.S. FDA . Treatment efficacy with these two antibiotics can vary , and antimicrobial resistance (especially to OTC) has been documented in some Fp strains. Therefore, research investigating the relationships betwe en antibiotic resistance in Fp , and in vivo virulence is imperative. Our lab tested t wo Fp strains (US57 and US87) showing varied in vitro antibiotic sensitivity against OTC and FFC. To evaluate the clinical relevance of antibiotic resistance in th e Fp strains, experimental challenges of rainbow trout fry were conducted by intramuscular injection (IM) Fp US57 or Fp US87 str ain with 105 CFU/fis h. Five days post-challenge, fish were fed at 1% body weight (BW)/d for 10 days on the oxytetracycline-medicated feed at high rate (3.75g/100lb fish) or low rate (2.0g/100lb fish), or florfenicol-medicated feed at high rate (15 mg/kg BW/day) or low (10 mg/kg BW/day), respectively. All treatment groups except for the mock-challenged fish had mortalities with symptoms of BCWD, but the cumulative percent mortality (CPM) varied significantly among treatments. FFC treatments significantly (p<0.01) reduced the mortality of rainbow trout infected w ith US87 strain, but only had a moderate inhibition effect on US57-challenged fish . Both US57 and US87 strains showed resistance to OTC as CPM was not different from untreated controls at either high or low treatment rates . Results from this study illustrate the importance of antibiotic sensitivity testing on Fp strain and point to the need to utilize antibiotic treatment judiciously for control of BCWD.