Antibiotics are considered an important primary therapy for bacterial diseases in aquaculture. This study evaluated the in uence of oral administration of oxytetracycline (OTC) on feed intake, growth, mortality, residue accumulation and clearance, and histopathological changes in the vital organs of six groups of Nile tilapia Oreochromis niloticus when fed at 0-10 times the therapeutic dose (1X: 80 mg/kg biomass/day) for 10 and 20 consecutive days. The feed intake was reduced only slightly, viz., 2% in 10 days and 4.25% in 20 days dosing trials at 1X-dose compared to control. While in other groups, an OTCdose-dependent reduction in feed intake up to 31.25% was noted. The sh of 0.5X and 1X groups recorded signi cantly high biomass; while the other OTC-dosed groups recorded signi cantly lower biomass than the control. The fold change in biomass between the control and 1X groups was insigni cant. A dosedependent mortalities were recorded in OTC-dosed sh in 10 days (1.67±2.89-6.67±2.89%) and 20 days (3.33±2.89-8.33±2.89%) trials. The OTC concentration in sh muscle established a dose-and timeresponse relationship. The OTC residue levels in muscle even on day 20 OTC-dosing were lower than the maximum residue limit permitted by Codex Alimentarius (200 ng/g). On day 23 post-OTC-dosing, the residue levels were traces to <10 µg/g in all groups, except the 10X group. The OTC-dosing caused mild to moderate pathological changes in the gills, liver and kidney of O. niloticus and the sh were able to mount adaptive biological responses to overcome the stress with time.