Oxidative stress induced by disturbed homeostasis of metal ions, including copper ions, is one of the mechanisms underlying the development of neurodegenerative diseases. As currently there is no effective treatment capable to prevent or slow their progression, potential new drugs are actively being investigated. Flavonoids are a group of natural compounds originating from plants. Considering their known antioxidant and antiapoptotic activity, it is assumed that they could be effective in slowing down or preventing neurodegenerative processes. The aim of this study was to investigate the effect of the flavonoid myricitrin on the survival of SH-SY5Y cells in oxidative stress conditions induced by toxic concentrations of copper ions. Contrary to expectations, myricitrin demonstrated a prooxidative effect, enhanced the neurotoxic effect of copper and further reduced cell survival. It stimulated production of reactive oxygen species and reduced intracellular glutathione and ATP levels. Decreased superoxide dismutase activity and aconitase inactivation also indicated its prooxidative action. Cell death was probably induced by apoptosis and necrosis as myricitrin increased caspase-3/7 activity, chromatin condensation and propidium iodide staining. The neurotoxic effect of myricitrin was increased in the presence of wortmannin, an inhibitor of the PI3/Akt signaling pathway, and decreased in the presence of BAPTA-AM, an intracellular calcium chelator, and MK-801, a blocker of N-methyl-D-aspartate glutamate receptors, indicating the important role of calcium ions in the initiation of cell death following exposure to copper and myricitrin.