Oxytetracycline (OTC) is a broad spectrum antibacterial agent approved for treating certain bacterial diseases in salmonids cultured in water temperatures greater than or equal to 9 °C. A prominent disease of juvenile salmonids is coldwater disease. Although coldwater disease may be effectively treated with OTC, this disease typically occurs at water temperatures below 9 °C. The study was conducted to provide the information necessary to expand the OTC label to include the treatment of diseased salmonids cultured at water temperatures below 9 °C. The study objectives were to determine the time after treatment (feeding fish OTC medicated feed) when the OTC concentration in the skin-on fillet tissue of juvenile coho salmon (Oncorhynchus kisutch) treated with OTC decreased to a concentration below the tolerance limit of 2000 ng/g and to determine the depletion rate for OTC in the skin-on fillet of juvenile coho salmon treated with OTC. To fulfill these objectives, juvenile coho salmon were cultured and fed OTC medicated feed at a rate of 88.2 mg OTC per kg body weight per day at water temperatures ranging from 4.1 to 8.5 °C on the Quilcene National Fish Hatchery (a U.S. Fish and Wildlife Service hatchery), located in Quilcene, WA. This rate of treatment was slightly greater than the maximum rate of 82.7 mg/kg/day designated on the label. Pairs of skin-on fillets were taken from individual fish sampled on days 4 and 10 during the treatment period, one day after the last treatment, then four, eight, 14, and 19 days after the last treatment. The OTC concentration in skin-on fillet samples were determined with a high performance liquid chromatography analytical method developed at the Upper Mississippi Science Center. The maximum mean OTC concentration was 932 ng/g one day after the last treatment day and the minimum mean OTC concentration was 32 ng/g observed 19 days after the last treatment day. The loss of OTC from the fillet tissue was biphasic with a terminal phase half-life of 4.9 days.