Copper oxide nanoparticles (NPs) are used in an expanding range of industries including a potential for agricultural applications as a fungicide. Accidental spills or misapplication of CuO NPs may lead to soil contamination. Plant roots exude a wide range of organic chemicals for bioprotection and to enhance bioavailability of nutrients. Many of these chemicals are metal chelators that may increase the solubility of CuO NPs, thus enhancing the impact of these NPs on plants. This work was directed towards understanding which plant exudates force increased solubility of CuO NPs and to determine if the level of NP in the growth matrix drives a feedback effect, regarding composition and quantity of exudates. Wheat seedlings (Triticum aestivum cv Deloris) were grown in a sand matrix for 10 days after 3 days of germination. The sand was amended with sublethal doses of CuO NPs from 0 to 300 mg Cu/kg dry sand. Sand was selected as the solid growth matrix as a proxy for soil in terms of plant root morphology, mechanical impedance and water stress, while providing a low background of dissolved organic carbon for the isolation of root exudates. After plant growth, the pore water was collected from the sand by vacuum filtration and analyzed. By coupling analytic techniques including Triple Quad Mass Spectroscopy and ion chromatography with geochemical modeling, we have identified citrate and the phytosiderophore, deoxymugineic acid (DMA) as chelators that drove the majority of dissolution of CuO NPs, especially DMA at higher CuO NP doses. Altered biogeochemistry within the rhizosphere was correlated with increased plant uptake of Cu and bio-response via exudate type, quantity and metal uptake. Exposure of wheat to CuO NPs lead to dose-dependent reduction in Fe, Ca, Mg, Mn and K in roots and shoots. This work is relevant to growth of commercially important crop wheat in the presence of CuO NPs as a fertilizer, fungicide or a pollutant.