This study was carried out to evaluate the use of Lactobacillus acidophilus as a biocontrol agent against some common fish pathogenic bacteria (Staphylococcus xylosus, Aeromonas hydrophila gr.2 and Streptococcus agalactiae) in African catfish, Clarias gariepinus. Eight treatments were designed inclusive of 10 C. gariepinus juveniles (mean weight 190 g) per tank, each in triplicate. Four groups of fish were fed a diet supplemented with L. acidophilus, comprising about 3.01 × 107 colony‐forming units per gram of diet (the probiotics diet), while the other four groups were fed a diet not supplemented with probiotics (the non‐probiotics diet). In the first group, fish were injected with 1 mL physiological saline and fed the non‐probiotic diet (non‐probiotic control); in the second, third and fourth groups, fish were injected with 1 mL each of S. xylosus, A. hydrophila gr.2 and S. agalactiae, respectively, and were all fed the non‐probiotic diet (designated as non‐probiotic treatments; NPsx, NPah and NPsa respectively). In the fifth group, fish were injected with 1 mL physiological saline but fed the probiotic diet (probiotic control), while fish in the sixth, seventh and eighth groups were each injected with 1 mL of S. xylosus, A. hydrophila gr.2 and S. agalactiae, respectively, and were all fed the probiotic diet (and designated as probiotic treatments; Psx, Pah and Psa respectively). Blood samples were collected for haematology analysis, while samples of the liver and kidney were examined for pathohistology after 7 and 21 days of infection. The results showed that the haematology parameters, packed cell volume, haemoglobin, erythrocyte sedimentation rate, red blood cell, white blood cell, total serum protein, Mg2+, Ca2+, Cl−, glucose, cholesterol and total immunoglobulin concentrations and the pathohistology of the liver and kidney were better in the challenged fish (infected) maintained on the probiotic diet than those in the groups fed the non‐probiotic diet. It is concluded, based on these results, that L. acidophilus is useful as a probiotic agent in C. gariepinus against these pathogenic bacteria (S. xylosus, A. hydrophila gr.2 and S. agalactiae).