Technical Abstract: Juvenile red drum Sciaenops ocellatus were exposed to sublethal waterborne copper (Cu) concentrations (0.25-0.35 mg/L Cu) using a chelated Cu compound for 242 days as a prophylactic treatment to control ectoparasites followed by a 21-day withdrawal period in two 43 m3 recirculating aquaculture systems. Skin, muscle, gills, liver and intestinal tissues were collected on days 1, 3, 5, 15, and 21 during the 21-day depuration. Liver and intestine accumulated Cu at a rate strongly influenced by the environmental Cu load. Skin, gill, and muscle tissue did not accumulate substantial amounts of Cu despite its presence at therapeutic levels. The rank order of Cu concentration in each tissue was intestine > liver > gills > skin > muscle. Predictive equations for tissue Cu concentration in ug/g relative to time of withdrawal (day) and waterborne Cu concentrations (mg/L) were generated using trend analysis. Red drum cultured in recirculating aquaculture systems had low (26-52 ug/g) detectable Cu concentrations in muscle tissue relative to wild caught red drum (414 ug/g). A 21-day withdrawal following prophylactic Cu treatments < or = 0.35 mg/L in red drum appears to be sufficient to meet the safety standards for human consumption.