In January 2008 there was an intensive and extensive upwelling event in the southern Humboldt Current System. This event produced an intrusion of water with low dissolved oxygen into Coliumo Bay, which caused massive mortality and the beaching of pelagic and benthic organisms, including zooplankton. During this event, which lasted 3 to 5 days, we studied and evaluated the effect of the hypoxic water in the bay on the abundance of macrozooplankton, nanoplankton and microphytoplankton, the concentration of several nutrients and hydrographic conditions. At the beginning of the hypoxia event the water column had very low dissolved oxygen concentrations (<0.5 mL O2 L-1), low temperatures and high salinity which are characteristics of the oxygen minimum zone from the Humboldt Current System. Redox, pH, nitrate, phosphate, silicate and chlorophyll-a values were the lowest, while nitrate and the phaeopigment values were the highest. The N:P ratio was below 16, and the abundance of nano- and microphytoplankton were at their lowest, the latter also with the lowest proportion of live organisms. Macrozooplankton had the greatest abundance during hypoxia, dominated mainly by crustacean, fish eggs and amphipods. The hypoxia event generated a strong short-term alteration of all biotic and abiotic components of the pelagic system in Coliumo Bay and the neighboring coastal zone. These negative effects associated with strong natural hypoxia events could have important consequences for the productivity and ecosystem functioning of the coastal zone of the Humboldt Current System if, as suggested by several models, winds favorable to upwelling should increase due to climate change. The effects of natural hypoxia in this coastal zone can be dramatic especially for pelagic and benthic species not adapted to endure conditions of low dissolved oxygen.