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The effects of dietary Lagnaria breviflora leaves extract (LBLE) on the growth performance, feed utilisation and haematological parameters of juveniles African catfish, Clarias gariepinus (mean = 8.45 ± 0.6 g) raised in a flow water (mean temperature 26.7°C, mean pH 7.52, mean dissolved oxygen 6.05 mg/L) were assessed in this study. Diets (400 g/kg crude protein; 4631.5 kcal/kg gross energy) supplemented with LBLE at levels of 0 (control), 0.5, 1.0, 1.5 or 2.0 g/kg diet were served to fish in triplicates (each replicate has 20 fish) until they appeared satiated for 12 weeks. Then, they were challenged with Aeromonas hydrophila infection for further 2 weeks. Fish served dietary LBLE had considerable higher weight gain (64.76 g) and specific growth rate (765.5% g/day) than the fish group fed with the control diet with a reduced feed conversion ratio (1.45) (p < 0.05). Compared to fish fed with the control diet, the villi height (146.30 µm) and width (284.35 µm) of the intestines increased greatly in a dose (LBLE in diets) dependent order. Similarly, dietary LBLE increased (p < 0.05) the packed cell volume (46.11%) and haemoglobin (17.03 g/dL), whereas 1.5 g of LBLE increased the counts of white blood cells. Glutathione S-transferase (769.43 U/mg protein), glutathione peroxidase (84.14 U/mg protein) and superoxide dismutase (433.15 U/mg protein) activities were significantly higher (p < 0.05) in fish fed with diets supplemented with LBLE compared to the control one. Additionally, dietary LBLE increased phagocytic and lysozyme activities and protected C. gariepinus against bacterial infections where the lowest death was observed in the fish fed on the diet containing 1.5 g LBLE/kg feed. These findings showed that the fish fed with LBLE/kg diet improved their immune system, antioxidant and growth performance in addition to providing protection from A. hydrophila infection with the optimum dose of 1.80 g/kg diet., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)