Background: Yellow grub (Clinostomum marginatum) infection severely impairs Nile tilapia productivity, causing growth retardation, hematological disorders, and increased susceptibility to secondary infections. Methods This study comprehensively evaluates the biosynthesis, characterization, and multifaceted biological activities of selenium nanoparticles (SeNPs) produced using Saccharomyces cerevisiae SA33, which MALDI-TOF identified as S. cerevisiae DSM 34246 and their effect in mitigating infections caused by Clinostomum marginatum. The antioxidant, antibacterial, and antiparasitic activities of SeNPs were determined using the DPPH assay, disc assay, and measuring parasite mortality, respectively. Results: UV-Vis spectroscopy confirmed the formation of SeNPs with a distinct absorption peak at 285 nm, and transmission electron microscopy (TEM) revealed well-dispersed, spherical nanoparticles with an average diameter of ~40 nm. Dynamic light scattering (DLS) and zeta potential analysis indicated a monodisperse size distribution (33 nm) and moderate colloidal stability (-22.35 mV). The biosynthesized SeNPs (200 µg/mL) exhibited potent dose-dependent antioxidant activity, scavenging over 90% of DPPH radicals. Antibacterial assay demonstrated significant growth inhibition against pathogenic bacteria. Antiparasitic activity of SeNPs against Clinostomum marginatum (Yellow Grub) reached >80% inhibition compared to praziquantel 75 %. In yellow grub-infected Nile tilapia, SeNPs (200 mg/kg diet) significantly enhanced growth performance, increasing final weight, weight gain, and feed efficiency, however, decreasing the FCR, while maintaining 100% survival. Hematological analysis of infected fish revealed SeNPs restored red blood cell counts, hemoglobin levels, and immune cell balance, counteracting parasitic anemia and inflammation. Serum biochemistry confirmed hepatoprotective effects, reducing stress markers (cortisol decreased from 9.89 to 1.90 µg/mL) and enhancing immune responses (lysozyme activity increased by 82%). Gene expression studies showed SeNPs upregulated growth-related genes (GHR) and myogenic regulators (MYOG, MYF6). Histopathological assessment demonstrated SeNPs' protective role, reversing gill damage (lamellar fusion, necrosis) caused by Clinostomum infection. Additionally, SeNPs reduced the bacterial count in water and fish organs. Conclusion: These findings highlight SeNPs as a versatile, eco-friendly nanomaterial with antioxidant, antimicrobial, antiparasitic, and growth-promoting properties, providing a sustainable solution for enhancing aquaculture health and productivity.

To Cite This Article: Albohiri HH, Alsulami MN, Al-Rashidi HS, Almayouf MA, Mogadem A, Aljohani AA, Mahjoub HA., Althagafi H, Sumayli M, Almasoudi SH, Ahmed AE, 2025. The influence of nutritional biological selenium nanoparticles (SeNPs) for controlling Clinostomum marginatum infection in Nile Tilapia (Oreochromis niloticus). Pak Vet J. http://dx.doi.org/10.29261/pakvetj/2025.251