Nile tilapia, Oreochromis niloticus (average initial weight, 5.91 ± 0.04 g), were fed four isonitrogenous and isolipidic diets for 84 days. The diets contained four levels of yeast extract (CW‐I) rich in nucleotides and β‐glucan: 0 (control), 5, 10 and 15 g/kg diet. Weight gain increased linearly, whereas the feed conversion ratio decreased linearly with increasing levels of yeast extract. The diet containing 15 g/kg yeast extract resulted in significantly better (p < 0.05) specific growth rates and protein efficiency ratios. No significant (p > 0.05) differences were found in dry matter, protein, lipid or ash contents or in haematocrit, haemoglobin or total protein contents among the treatment groups. Blood sample profiles showed an increase in white and red blood cells in fish fed 15 g/kg yeast extract in comparison with the other treatment groups. The fish fed the diets with 10 and 15 g/kg yeast extract had significantly higher albumin and globulin levels than the control group, whereas decreased levels of cholesterol and triglycerides, aspartate aminotransferase and alanine aminotransferase were noted in fish fed the diet with 15 g/kg yeast extract. Histological analysis of the liver and intestine in fish fed the control diet showed a slightly abnormal structure in these organs. Only in fish fed diets supplemented with the highest amount of yeast extract was the structure of the hepatocytes and villi almost unchanged, which indicated that the yeast nucleotides could improve hepatic function and promote liver and gut restoration.