BACKGROUND: Over the years, nanoparticles have emerged as a promising approach for improving crop growth, yield, and overall agricultural sustainability. However, there has been growing concern about the potential adverse effects of nanoparticles in the agricultural sector and the environment. The present study aimed to investigate the detrimental effects of high (1000 mg L RESULTS: The results showed a CuO NPs treatment led to an impairment of nutrient balance in barley leaves. An increase in hydrogen peroxide content followed by the higher specific activity of catalase and ascorbate peroxidase was also observed in response to CuO NPs, CuO bulk, and Cu CONCLUSION: Our findings suggest that the systemic resistances in barley seedlings were induced by higher accumulation of ABA, ET, and JA under CuO NPs treatment. The activation of systemic resistances indicated the involvement of both SAR and SAR pathways in the response to CuO NPs in barley.