•Prebiotic based on β-glucans, glucomannans and MOS, at lower levels, showed an analogous effect to chlorohydroxyquinoline (positive control).•The antimicrobial treatment provided a better feed conversation.•Chlorohydroxyquinoline and β-glucans, glucomannans and MOS increased spleen weight.•The higher level of the prebiotic (3000 mg/kg) reduced the jejunal villus density. This study proposes to evaluate the addition a prebiotic product based on beta-glucans (β-glucans), glucomannans, and mannan oligosaccharides (MOS), replacing an antimicrobial growth promoters in diets for newly weaned piglets, on their performance, occurrence of diarrhea (OD), hematological parameters, organ morphometry, pH of the digestive content, and intestinal epithelium morphology. The experiment involved 120 piglets weaned at 21 days of age, with an initial weight of 6.35 ± 0.10 kg, which were allotted to five treatments in a completely randomized block design with six replicates and four piglets per experimental unit. The following treatments were: 0 – basal diet; 1000, 2000, or 3000 mg/kg of a prebiotic; and ANT – basal diet with 120 mg/kg chlorohydroxyquinoline. The inclusion of prebiotic levels in the diet caused a worsening (P < 0.05) in feed conversion (FC). Hematological analysis revealed that prebiotic levels in the diet provided a quadratic effect (P < 0.05) in eosinophil count. The antimicrobial treatment provided a better FC (P < 0.05). Prebiotic levels elicited a quadratic response from villus density (VD) in the duodenum and, in the jejunum, VD decreased linearly (P < 0.05). The ANT treatment led to a lower VD (P < 0.05), in duodenum, compared with treatment 3000 mg/kg. In the jejunum, VD increased (P < 0.05) in ANT when compared with 1000 and 3000 mg/kg of prebiotic. Based on the present results, 3000 mg/kg of a prebiotic are not a viable alternative to performance-enhancing antimicrobials in the diet of piglets.