The broad-spectrum antibacterial drug oxytetracycline (OTC) is used in the U.S. to treat certain diseases in salmonids and catfish. This study was conducted to support an extension of the OTC label to include all cool-water fish species cultured at U.S. public aquaculture facilities by satisfying human food safety requirements. Juvenile northern pike (Esox lucius; mean weight: 117 g) and walleye (Stizostedion vitreum; mean weight: 59 g) were fed OTC-medicated diets near the maximum legal treatment rate (82.7 mg OTC-HCl/kg fish/day for 10 days) and near the lower limit of the water temperature range for most disease outbreaks in these species (14 and 16 °C, respectively). Two trials were conducted simultaneously with northern pike, one using commercially medicated feed and the other using on-site OTC top-coated feed. A third trial was performed with walleye using on-site OTC top-coated feed. Fillet tissues were collected and OTC free base (OTC-base) concentrations were determined by high performance liquid chromatography. The maximum mean OTC-base concentrations in the fillet tissue were 319 ng/g in northern pike (skinless) and 721 ng/g in walleye (skin-on), both well below the current tolerance limit of 2000 ng/g OTC-base. The log-linear loss of OTC-base from the fillet tissues was monophasic, with terminal phase half-lives of 5.9 days in northern pike fed commercial medicated feed, 6.7 days in northern pike fed top-coated feed, and 10.5 days in walleye fed top-coated feed. The data supported a zero withdrawal time in juvenile northern pike and walleye fed OTC at the approved dose level for 10 days at water temperatures down to 14 and 16 °C respectively.