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The present study assessed the toxic effect of super-paramagnetic iron oxide nanoparticles (SPIONs) on haemato-immunological responses, antioxidant capacity, oxidative stress, and metabolic enzyme activities in Labeo rohita fingerlings, as well as the possible ameliorative effect of dietary vitamin E. The experiment was conducted for 30 days (15-day exposure and recovery each) under static bioassay. The LC50 concentration of SPIONs was estimated by 96-h exposure which was 3253.20 mg/L. The fishes were distributed in two groups and exposed to three levels 1/50th, 1/25th, and 1/10th of SPION-LC50 concentration. Group 1: fed with control diet and referred to as CS0, CS/50, CS/25, and CS/10, while group 2: fed vitamin E supplemented diet and referred to as ES0, ES/50, ES/25, and ES/10. Significant alterations were observed in haemato-immunological responses, malondialdehyde (MDA), and oxidative and metabolic enzymes activity even after supplementation of vitamin E. The exposure to SPIONs altered haemato-immunological parameters, MDA accumulation, and tissue enzyme activity, i.e., superoxide dismutase (SOD), catalase (CAT), glutathione s-transferases (GST), xanthine oxidase (XO), lactate dehydrogenase (LDH), and malate dehydrogenase (MDH) in a dose-dependent manner. However, they relapsed to the level of control in S/50 exposed group at the end of the recovery period. The dietary vitamin E shows significant toxicity mitigating effect during the recovery period. Thus, SPIONs can be used up to a concentration of 65.06 mg/L in the culture water of Labeo rohita and its toxicity at higher doses can be partially ameliorated by feeding of vitamin E (at 250 mg/kg feed) for 15 days during post exposure period. Highlights: • The toxicity of SPIONs increased with increasing concentration of nanoparticle. • The lethal concentration (LC50) of SPIONs was 3253.20 mg/L. • At the end of the recovery period, dietary supplementation of vitamin E ameliorate toxic effect of SPIONs. • The physiological change caused due to the toxic effect of 65.04 mg/L SPIONs can be completely recovered in 15 days by dietary supplementation of vitamin E at 250 mg/kg in L. rohita. [ABSTRACT FROM AUTHOR]