Aerosol deposition plays an important role in climate and biogeochemical cycles by supplying nutrients to the open ocean, in turn stimulating ocean productivity and carbon sequestration. Aerosol particles also contain elements such as copper (Cu) that are essential in trace amounts for phytoplankton physiology but that can be toxic at high concentrations. Although the toxicity of Cu associated with aerosols has been demonstrated in bioassay experiments, extrapolation of these laboratory results to natural conditions is not straightforward. This study provides observational evidence of the negative effect of aerosols containing high Cu concentrations on marine phytoplankton over a vast region of the western Mediterranean Sea. Direct aerosol measurements were combined with satellite observations, resulting in the detection of significant declines in phytoplankton biomass after atmospheric aerosol events characterized by high Cu concentrations. The declines were more evident during summer, when nanoflagellates predominate in the phytoplankton population and stratification and oligotrophic conditions prevail in the study region. Together with previous findings concerning atmospheric Cu deposition, these results demonstrate that the toxicity of Cu-rich aerosols can involve large areas of the world’s oceans. Moreover, they highlight the present vulnerability of oceanic ecosystems to Cu-rich aerosols of anthropogenic origins. Because anthropogenic emissions are increasing, large-scale negative effects on marine ecosystems can be anticipated.