Prunus armeniaca (apricot) kernel as a plant by-product, has garnered a lot of attention lately due to its biological and medicinal properties. This study represents a novel attempt to supplement Nile tilapia (Oreochromis niloticus) diets with the P. armeniaca kernels (PK) powder. This approach evaluated its effectiveness on growth, digestive/ absorptive capabilities, economic efficiency, physiological/antioxidant status, and immune capacity. Additionally, the expression of nutrient transporters, lipid metabolism, and immune-relevant genes as well as the fish resistance to the Pseudomonas putida challenge were investigated. Fish (n = 160; 21.70 ± 0.22 g body weight) were allotted for a 3-month feeding trial into four treatments (n = 40 fish/treatment) in quadri-replicates (10 fish/replicate). The fish in each treatment were fed on a basal diet fortified with 0, 2, 4, and 8 g of PK/kg diet (PK0, PK2, PK4, and PK8), respectively. The outcomes revealed that all PK-enriched diets boosted growth indices (weight gain, specific growth rate, and protein efficiency ratio), growth hormone level, and intestinal enzyme activity (lipase and amylase). The PK-fortified diets improved intestinal morphometric indices (muscular coat thickness and villus width and length) and declined feed cost/kg gain. This enhancement was in a leveldependent manner with the PK8 treatment presenting the best results (P < 0.05). Up-regulation of the intestinal nutrient transporters-associated genes (solute carrier family 15 member 2, solute carrier family 9 member 3, and sodium-glucose cotransporter 1) was observed in PK-fed treatments. The expression of muscular lipid metabolism-relevant genes was modulated by the dietary PK, where lipid deposition-relevant genes (acetyl-coenzyme A carboxylase beta and sterol regulatory element-binding protein 1) down-regulated, while the lipolysisrelevant gene (carnitine palmitoyltransferase 1) up-regulated. The antioxidant-immune responses (glutathione peroxidase, catalase, total antioxidant capacity, total protein, globulin, serum bactericidal activity, nitric oxide, and complement3) were augmented by dietary PK inclusion with increasing PK dietary levels. Moreover, the expression of splenic immune-related genes (nuclear factor kappa beta, interferon-gamma, and Kelch-like ECHassociated protein1) was up-regulated by PK diets. Post-challenge with P. putida, the fish survival rate in PK8 treatment (87.50 %) was the highest followed by PK4 (81.25 %), and PK2 (75.00 %) treatments compared to PK0 treatment (56.25 %). Overall, it is advised to feed Nile tilapia with the PK-supplemented diets to enhance their growth, immune response, and resistance to P. putida. This provides an outline for the future use of these seed kernels for supporting the aquaculture sector.