The direct impact of oxidation–reduction potential (ORP) on fish welfare and water quality in marine recirculating aquaculture systems (RAS) is poorly documented. In this study, the effects of the fish size (S1, S2, S3) and ORP level (normal, four successive levels) on the performance of European sea bass (Dicentrarchus labrax) were investigated. Three size fish were distributed into two RAS (RAS and RAS O3). Ozone was injected into RAS O3 to increase the ORP level. The ORP was stabilized to four successive levels: 260–300, 300–320, 320–350, and 300–320 mV in fish tanks during four periods (P1–4). At the last day of each period, the hematological parameters, plasma protein and mortality of sea bass were analyzed. Two-way ANOVA revealed that several hematological parameters, including pH, hematocrit, concentrations of oxygen, carbon dioxide, glucose (Glu), ionized calcium, kalium, and hemoglobin, were significantly influenced by the increased ORP levels over the experimental period. The alteration in blood Glu and plasma protein concentration showed that ORP around 300–320 mV started to stress sea bass. Once the ORP exceeded 320 mV in the tanks during the P3 period, mortality occurred even when total residual oxidants/ozone-produced oxidants was only 0.03–0.05 mg L−1 in the fish tanks. At the same time, plasma protein decreased notably due to appetite depression. After the decrease in ORP during the P4 period, mortality continued. In conclusion, the results strongly suggest that for European sea bass in RAS, the ORP should not exceed 320 mV in the tanks. Once ozonation damaged fish, the effect seemed to be irreversible. However, how ORP affected related hematological parameters still need the further investigations.