Factors such as stocking density can influence free radical production and antioxidant defense mechanisms. However, this information is still unknown for many freshwater species of zootechnical interest, including the pirapitinga (Piaractus brachypomus). The objective of this study was to investigate the effects of stocking density on the oxidative status of P. brachypomus juveniles. A total of 108 juveniles (250.35±13.52 g) were reared for 90 days in a completely randomized design with three stocking densities (1.5, 3.0, and 4.5 kg m⁻³), fed twice a day with a commercial extruded diet containing 36% crude protein. The results showed that lipid peroxidation, assessed by TBARS, was unaffected by stocking density in both liver and muscle (p>0.05), and the same was observed for ascorbic acid and total protein content in both tissues (p>0.05). In contrast, the enzymatic and non-enzymatic components of the antioxidant system were modulated in a tissue-specific manner. In the liver, a coordinated upregulation was observed at the highest density (D4.5), with higher SOD activity (p<0.05), GST activity (p<0.05), and GSH content (p<0.05) compared to D1.5. Hepatic CAT activity, however, followed a different pattern, peaking at the intermediate density (D3.0) and being lower at both D1.5 and D4.5 (p<0.05). In the muscle, SOD activity was highest at D1.5 and reduced at D3.0 and D4.5 (p<0.05), whereas GST activity (p<0.05) and GSH content (p<0.05) peaked at the intermediate density (D3.0). Muscular CAT activity was not affected by stocking density (p>0.05). The highest density tested elicited a coordinated remodeling of the hepatic antioxidant system and modulation of purinergic signaling in the cephalic kidney, in the absence of lipid peroxidation, suggesting an integrated adaptive response. Therefore, under the conditions of the present study, these stocking densities can be considered suitable for the cultivation of P. brachypomus in an RAS. Acknowledgments: This research was funded by CNPq-Brasil – 402840/2023-2, 310170/2023-0, 301816/2022-0, and 316901/2021-0).