Mycotoxins, originating from contaminated raw materials or suboptimal feed storage, are a growing concern in tropical aquaculture. Common fungi such as Aspergillus spp. and Fusarium spp. produce mycotoxins including aflatoxin, fumonisin, deoxynivalenol and zearalenone. High doses or prolonged exposure (weeks) to low doses of these mycotoxins (< 20 μg/kg) can depress growth, immunity, and cause mortality. This study investigated poor growth and low survival in juvenile Asian seabass, Lates calcarifer fed two different diets (FM40 and ABS3) for 5 weeks. Analysis of these diets revealed high peroxide values, multiple mycotoxins and high histamine levels. Fish fed the FM40 diet, which was contaminated with aflatoxin B1 (13.2 μg/kg), aflatoxin B2 (1.9 μg/kg), deoxynivalenol (29.5 μg/kg), alternariol (2.2 μg/kg), elevated peroxide value (45.91 mEq/kg), and histamine (129.51 mg/kg) developed mild bile duct hyperplasia, depressed total serum proteins (50.40 ± 10.06 g/L), markedly elevated blood potassium (8.2 ± 0.18 mmol/L), and heavy iron deposits in splenic melanomacrophage centres (Perl's stain) indicative of increased haemolysis. The presence of multiple cytotoxic mycotoxins in FM40 diet could explain the increased haemolysis and elevated blood potassium. In contrast, fish fed the ABS3 diet, which had high histamine levels (210.05 mg/kg), exhibited protein‐losing nephropathy with multifocal fibrin plugs (Martius scarlet blue stain) indicating acute renal damage, and elevated blood calcium and phosphorus levels. Histamine is metabolised and excreted through the kidneys and known to induce renal arteriolar constriction, disrupt glomerular filtration barrier and increase permeability resulting in protein loss. This study shows that blood biochemistry and histopathology are useful diagnostic tools for assessing the impact of mycotoxins and histamines on fish health.