The abuse of antimicrobial has raised more and more attention in recent years because of its severe harm on environments and human health caused by the drug residues. In this study, we investigated the effects of florfenicol on immune and antioxidant activities of the Exopalaemon carinicauda by measuring the concentration of HEM and the activities of ACP, AKP, T-SOD, CAT and T-AOC in the plasma of E. carinicauda in the presence of florfenicol at different concentrations. At 3 h, the HEM concentration of the samples treated with low/medium dose of florfenicol (10 or 20 mg/kg·BW) was significantly higher than that of the control group (P<0.05); from 3 h to 48 h, high dose of florfenicol (40 mg/kg·BW) had the same effect (P<0.05). At 3 h and 6 h, the ACP activity in the presence of low/medium dose of florfenicol was higher than that of the control group (P<0.05); from 3 h to 168 h, high dose of florfenicol reduced the ACP activity (P<0.05). In the presence of low/medium dose of florfenicol, the activity of AKP was higher than the control at 3 h (P<0.05), from 6 h to 48 h, however, it decreased to a lower level than the control (P<0.05). At the end of the three experiments described above, all the values of the experimental groups returned to the control level. When treated with low/medium dose of florfenicol, the activity of T-SOD was higher than the control and peaked at 6 h and 24 h; in the contrast, the T-SOD activity was lower than the control at 24 h and 48 h when treated with high dose of florfenicol (P<0.05). Regardless of the florfenicol concentration, the activity of CAT was higher than the control at 3 h and 6 h (P<0.05), but was lower than the control group from 12 h to 96 h (P<0.05), and then recovered to the control level at the end of the experiment. Florfenicol at all three concentrations caused a decrease in the T-AOC activity up to 96 h (P<0.05) in a dose-dependent manner. Our results suggested that these parameters discussed above could serve as potential biomarkers to evaluate the safe use of florfenicol in the culture of E. carinicauda.