Accumulation and elimination of enrofloxacin and its metabolite ciprofloxacin were evaluated in Exopalaemon carinicauda following medicated feed at dose of 10 mg/kg weight body per day for five consecutive days and 10 mg/L bath for five consecutive days at 18 °C. At different times, nine ridgetail white prawns were randomly selected from the tank and sampled after the last medicated feed or bath administration. The concentration of enrofloxacin and ciprofloxacin in the main tissues (hepatopancreas, muscle, gill, and ovary) was detected by HPLC. The results showed that the maximum concentrations of enrofloxacin were 3.408 ± 0.245, 0.554 ± 0.088, 0.789 ± 0.074, and 0.714 ± 0.123 μg/g for hepatopancreas, muscle, gill, and ovary, respectively, at 1 day after the last medicated feed treatment. The enrofloxacin concentrations were 2.389 ± 0.484, 0.656 ± 0.012, 0.951 ± 0.144, and 3.107 ± 0.721 μg/g in hepatopancreas, muscle, gill, and ovary, respectively, at 1 day after the last bath administration. Ciprofloxacin could be detected in hepatopancreas, muscle, gill, and ovary. However, the concentrations of ciprofloxacin were much lower in comparison with that of enrofloxacin in various tissues. The concentrations of enrofloxacin plus ciprofloxacin in hepatopancreas, muscle, gill, and ovary followed an eliminating pattern during the sampling time after the two routes of administration. Based on data derived from this study, to avoid the enrofloxacin and ciprofloxacin residue in E. carinicauda, it should take at least 20 and 25 days to wash out the drug from the tissues after the last medicated feed and bath administration with enrofloxacin, respectively. These results helped the Chinese fishery department to lay down the current guidelines on enrofloxacin plus ciprofloxacin withdrawal periods for farmed shrimp.