ABSTRACT This study evaluated the efficacy of aqueous monovalent vaccine (AqMV) and adjuvant monovalent vaccine (AdMV), different levels of soursop leaves (SL), and turmeric rhizome (TR) on growth performance, immune response, and disease resistance of African sharptooth catfish (Clarias gariepinus) fingerlings against Pseudomonas aeruginosa. The experimental diet consists of control (without vaccine, soursop leaves and turmeric rhizome), AqMV2, AdMV3, TR4 (0.5), TR5 (1.0), TR6 (2.0), SL7 (0.5), SL8 (1.0) and SL9 (2.0). Fish were exposed to 4.85 log10 CFU/ml P. aeruginosa of 24 h old culture intraperitoneally after feeding trial with relative level of protection recorded at 28 days of post-infection. The results revealed that fish fed with treated diets showed increased (p < .05) weight gain, feed conversion ratio, nitrogen metabolism, white blood cell, globulin, total protein and blood performance and better relative level of protection compared to the control. The microbial loads in fish samples (muscle, spleen and kidney) were reduced (p < .05) in the treatments when compared to the control at 4-week post-infection. These results suggest that inactivated aqueous monovalent vaccine, soursop leaves and turmeric rhizome could be effective against P. aeruginosa infection in fish farming.