The study was conducted to investigate the organ-specific antioxidants and protein damages responses in Lates calcarifer inhabiting different aquaculture farms that susceptible to different threat of pollutions. Enzymes at the front line of antioxidant system superoxidase dismutase (SOD) and catalase (CAT) evidenced to work together but respond differently in different body compartment. High SOD responses were followed with lower CAT responses observed in muscle (p < 0.05) with opposite responses exhibited by both gill and liver. The responses of SOD and CAT in muscle also showed a significant strong correlation to each other (Setiu Wetland: 0.91, Semerak: 0.79) (p < 0.01). The glutathione-dependent enzymes, glutathione-s-transferase (GST) and glutathione reductase (GR) in body compartments responded with a strong correlation to each other especially in muscle (Tumpat; muscle: 0.89, gill: 0.95 and liver: 0.54 (p < 0.01, p < 0.05), (Setiu Wetland; muscle: 0.72 (p < 0.01) and Semerak; muscle: 0.79 (p < 0.01). Opposite results were found for both protein damages biomarkers, thiols (-SH-) and carbonyl (-CH-) in comparison to biomarkers responses. In contrary to (-SH-) inconsistent results were observed for the (-CH-) with muscle found to be most oxidised. The responses of SOD, CAT, GST, GR, thiols and carbonyl were all computed into the same scale through Integrated Biomarker Score (IBR) to classify each aquaculture farms based on biomarkers responses. There was a slight variation in deviation score (A) between organs within the range of (5-7). However, Tumpat overall showed the highest IBR score and significantly higher (p < 0.05) than Setiu Wetland with a total score of combining responses score in all three organs (IBR: 84, muscle: 31, gill: 24, and liver: 29) followed by intermediate score in Semerak (IBR: 72, muscle: 23, gill: 23 and liver: 26) and Setiu Wetland (IBR: 59, muscle: 18, gill: 23 and liver: 18). These results indicated that the responses of antioxidant enzymes and protein damages in L.calcarifer from different organs are heterogeneous. Therefore, biomarkers should be selected based on their sequential groups in the antioxidant system for a better explanation of the oxidative stress evaluation in fish.