CuO and ZnO nanoparticles (NPs) have antimicrobial effects that could lead to formulations as pesticides for agriculture or medicine. The responses of two soil-borne plant pathogenic Pythium isolates to the NPs were studied to determine the potential of these metal oxide NPs as pesticides. Growth of the P. ultimum isolate was more sensitive to CuO NPs than the P. aphanidermatum isolate. Growth in liquid medium with CuO NPs eliminated culturability whereas exposure to ZnO NPs resulted in stasis with growth resuming on transfer to medium lacking NPs. The citrate in the medium used for the growth assays was involved in enhanced release of the toxic metals from the NPs. Both CuO and ZnO NPs affected processes involved in Fe uptake. The NPs reduced levels of Fe-chelating siderophore-like metabolites produced by Pythium hyphae. CuO NPs inhibited, but ZnO NPs increased, ferric reductase activity detected at the mycelial surface. These findings illustrate that the toxicity of the metal oxide NPs towards Pythium was influenced by the medium, especially by the presence of a metal chelator. Environmental factors are likely to alter the pesticide potential of the metal oxide NPs when formulated for agricultural use in soils.