The current oxytetracycline (OTC) label restricts the administration of OTC to control specific diseases of salmonids and catfish. In a comprehensive effort to gain broad approval for multi-species with multi-diseases for OTC, representative fish species from a family were chosen to conduct study to satisfy the human food safety requirements. Northern pike (Esox lucius) was chosen because it represents a primitive, cool water species cultured by public aquaculture. In this study, juvenile northern pike were divided into two groups and two residue depletion tests were conducted simultaneously. The tank size, water quality, and water temperature (13.8 ± 0.1 °C) were identical for both groups of fish. The first group of fish was offered a commercially prepared OTC incorporated trout diet (BioDiet Grower; 70.9 mg/kg/day OTC-HCl) at a rate of 2.4% of the total fish body weight per day for ten days. The second group was fed of a slow sinking walleye diet top-coated with OTC (Walleye Grower 9206; 94.2 mg/kg/day OTC-HCl) at a rate of 2.6% of the total fish body weight per day for ten days. On days 11, 12, 14, 16, 18, and 20 of the study, fish from both tanks were sampled and their skin-off fillets were analyzed for OTC-base concentration. Elimination of OTC-base from the fillet tissues of both groups was similar. The maximum mean OTC-base concentrations in the fillet tissues of northern pike fed medicated BioDiet Grower (203 ng/g) or medicated Walleye Grower 9206 (319 ng/g) remained below the current OTC-base tolerance limit of 2000 ng/g. Loss of OTC- base from the fillet tissues of both groups was monophasic. Elimination half- lives were 5.9 days for fish fed BioDiet Grower and 6.7 days for fish fed Walleye Grower 9206. The OTC-base concentration representing the one sided upper tolerance limits for the non-central t-distribution of the data, at the 95% confidence level with a 99% confidence interval, for fish fed BioDiet Grower (303 ng/g) and for fish fed Walleye Grower 9206 (502 ng/g) were under the tolerance limit for OTC-base in fillet tissue.