This study was conducted to compare the effects of commercially available (C) and greensynthesized (GS) Zinc oxide nanoparticles (ZnO-NPs) on immunological responses of common carp(Cyprinus carpio) skin mucus. GS ZnO-NPs were generated usingThymus pubescentand characterizedby UV–vis diffuse reflectance spectroscopy (DRS), Fourier-transform infrared spectroscopy (FTIR),X-ray powder diffraction (XRD), scanning electron microscope (SEM), and energy-dispersive X-rayspectroscopy (EDX). Fish (n= 150) were randomly allocated into five groups in triplicate and receiveda waterborne concentration of 0% (control), 25%, and 50% of LC50 96 h of commercially available (C1and C2) and green synthesized ZnO-NPs (GS1 and GS2) for 21 days. Results from XRD displayedZnO-NPs with 58 nm in size and UV-vis DRS, EDX, and FT-IR analysis showed that some functionalgroups from plant extract bonded to the surface of NPs. The SEM images showed that ZnO-NPs haveconical morphology. Acute toxicity study showed a higher dose of LC5096hfor green synthesizedZnO-NPs (78.9 mg.L−1) compared to the commercial source (59.95 mg.L−1). The highest activity oflysozyme and alternative complement activity (ACH50) were found in control and GS1 groups. Asignificant decrease in alkaline phosphatase activity (ALP) was found in C1 and C2 groups comparedto other treatments. Protease activity (P) was significantly decreased in the C2 group compared tothe control and GS groups. Total immunoglobulin (total Ig) content was the highest in the control. Inaddition, total Ig in the GS1 group was higher than GS2. The exposure to ZnO-NPs lowered totalprotein content in all experimental groups when compared to control. Present findings revealedlower induced immunosuppressive effects by green synthesized ZnO-NPs on key parameters of fishskin mucus