This study examined the effects of a combination of adjuvant monovalent vaccination (AdMV), aqueous monovalent vaccine (AqMV), soursop leaves, and turmeric rhizome on the growth performance, survival rate, and immuno-health status of Clarias gariepinus fingerlings following Pseudomonas aeruginosa challenge. Twenty C. gariepinus fingerlings (4.91 ± 0.01 g) were fed a diets consist of the control (0%), AqMV2 (0%), AdMV3 (0%), (AqMV+TR)4 (1.0%), (AdMV+TR)5 (1.0%), (AqMV+SL)6 (1.0%), (AdMV+TR)7 (1.0%), (AqMV+TR+SL)8 (2.0%), and (AdMV+TR+SL)9 (2.0%) for 84 days. The fish were fed twice daily at 3% body weight. The weight gain (WG), specific growth rate (SGR), white blood cells (WBC), lymphocytes, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total protein (TP) levels were examined. C. gariepinus fingerlings were induced with 4.85 log₁₀ CFU/mL of P. aeruginosa from a 24-hour-old culture intraperitoneally, mortality and relative survival percentage were recorded 28 days post-infection. The findings indicate that WG, and SGR, were better in the control group than all other treated groups except AdMV2. The treated groups showed higher WBC, lymphocyte, TP, and albumin levels when compared to the control. A reduction was noted in the kidney, muscle, and spleen bacterial counts in the treated groups compared with the control, and a drop in the AST and ALT values of the treated groups relative to the control. The treated groups showed lower mortality and better relative percentage of survival. These findings indicate that vaccination, turmeric rhizome, and soursop leaves together enhanced the growth, health metrics, and survival rate of C. gariepinus fingerlings against P. aeruginosa.