A 5-week feeding trial was conducted to evaluate the effects of biofloc in situ and commercial probiotic supplementation on white shrimp (1.87 ± 0.03 g) inorganic nitrogen control, growth, and immunophysiological response. For this purpose, four treatments were conducted: clear water with no probiotic application (CW), clear water with probiotic application (CW+P), biofloc with no probiotic application (FLOC), and biofloc with probiotic application (BFT+P); each group had three replicates. Growth parameters (final body weight, daily weight gain, specific growth rate) were significantly higher in the two biofloc systems (P < 0.05), and the FLOC and FLOC+P group did not have a significant difference (P > 0.05). The immune responses (total hemocyte count, complement component protein, and lysozyme) and antioxidant status (glutathione, catalase) in the CW+P, FLOC, and FLOC+P groups were increased significantly at the end of the experiment compared with the CW group (P < 0.05), and the FLOC and FLOC+P groups did not have a significant difference (P > 0.05). Results of a 10-day Vibrio harveyi challenge test show that the survival rates in CW+P, FLOC, and FLOC+P groups were significantly higher (P < 0.05), and the FLOC and FLOC+P groups did not have a significant difference (P > 0.05). These results suggest that probiotic addition in the biofloc system had little advantage, but probiotics can improve the immune status of the shrimp in the clear water system. Further, cost-effectiveness analysis showed that the biofloc system was an efficient and economical option for the production of white shrimp.