Immunostimulants have been found to be attractive and promising agents for disease management in aquaculture. The current study aimed to assess the impacts of feeding with Spirulina platensis (SP) and Salvia officinalis (SO) for 28 days on the immune status of Nile tilapia (Oreochromis niloticus). A total of 180 Nile tilapia (30.6 ± 0.12 g) were divided into 3 groups (triplicates of 20 fish/group). Control group was fed on a basal diet only, while the other two groups were supplemented with SP (10 gm/kg diet) and SO (7.5 gm/kg diet) respectively. Both of SP and SO showed in vitro antimicrobial activity against Pseudomonas aeruginosa. The immune response of Nile tilapia supplemented with SP and SO revealed significant increases in lysozyme, nitric oxide activities and IgM titer with enhancement of IL-1β and TNF-α genes expression before and after infection with P. aeruginosa.  Fish challenged with P. aeruginosa showed signs of infection with high mortality rate and low relative percentage survival which elevated to be 83% in SP group and 75% in SO group. It could be concluded that dietary supplementation with SP and SO improved immune response and protected Nile tilapia against infection.Moreover, SP showed better results than SO before and after infection.