High-density aquaculture produces oxidative stress that affects fish welfare and leads to poor growth. Agavin is a fructan that regulates the antioxidant response and inhibits stress-related alterations in blood metabolites (cortisol and blood lipids), preventing oxidative damage in fish. This study evaluated the effect of dietary agavin on the hepatic antioxidant response and blood metabolites in Nile tilapia under high rearing density. A negative control, a positive control, and experimental diets supplemented with 20 and 40 g/kg agavin were formulated. Nile tilapia (1.04 g ± 0.01 g initial body weight) were fed for 80 days to evaluate the antioxidant response and blood metabolites. After 90 days, fish were exposed to high density (63 kg/m³) for twenty days, except for the negative control (low-density). Under high-density stress, cortisol, cholesterol, and triglyceride levels decreased in fish fed diets with agavin compared with the positive control (high density). CAT and SOD activity significantly increased in fish fed agavin diets; malondialdehyde levels decreased under high density compared with both controls. These results suggest that dietary agavin supplementation promotes the antioxidant response and prevents stress-related alterations in blood parameters in Nile tilapia under high rearing density through its antioxidant properties and, probably, has a prebiotic effect.