Seaweed is an inherently important entity in marine ecosystems. It is not only consumed by aquatic animals but also improves environmental quality in the mariculture. Seaweed is also part of the diet of human beings. The purpose of the present study was to evaluate the antagonism of selenium (Se)-enriched Gracilaria lemaneiformis against heavy metals, specifically, the potential of dietary Se-enriched Gracilaria to protect against heavy metal toxicity in rabbitfish (Siganus oramin). Growth rate, heavy metal (Se, Cd, Pb, Cu, Zn and Cr) concentrations, malondialdehyde (MDA), metallothionein (MT), and the activity of the antioxidants, glutathione peroxidase (GPX), catalase (CAT) and superoxide dismutase (SOD) were all assessed. The results showed that the total organic and inorganic Se concentration for the 250 mg L Se-enriched Gracilaria was significantly higher than those of the 50 and 10 mg L treatments after 3 days of enrichment. The mean total Se concentrations in Gracilaria were 42.5 μg g in the 250 mg L treatment, 13.5 μg g in the 50 mg L treatment and 2.5 μg g in the 10 mg L treatment, respectively. Organic Se accounts for 80-82% of total Se in Se-enriched Gracilaria. The Se concentration of rabbitfish fed Se-enriched Gracilaria was significantly higher than control. Furthermore, Se increased Cu and Zn absorption, and enhanced MT generation, and improved GPX, CAT, and SOD antioxidant activity, and decreased MDA concentrations and lipid peroxidation levels, all antagonistic to Cd, Pb and Cr. The effects of Se-enriched Gracilaria on waterborne Cd, Pb and Cr-induced toxicity occurred via both enzymatic and non-enzymatic antioxidative mechanisms in rabbitfish. Selenium had synergistic effects on Zn and Cu in rabbitfish. For the 50 mg L Se-enriched Gracilaria treatment, the Se, Cu, Zn, and antagonistic Cd, Pb, Cr, and the antioxidant enzymes CAT, SOD, GPX activities, and MT concentrations in rabbitfish were higher than that with the 250 mg L and 10 mg L Se-enriched Gracilaria treatments. The 50 mg L Se treatment of Gracilaria was deemed to be the optimum concentration to promote growth of rabbitfish. Therefore, the obtained results suggest Se-enriched Gracilaria can antagonize heavy metal toxicity, and is an advisable Se supplement to improve the edible safety of cultured animals.Copyright © 2020 Elsevier Inc. All rights reserved.