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Projections of general circulation models suggest that freshwater discharge from the Mississippi River to the coastal ocean will increase 20% if atmospheric CO2 concentration doubles. This result is likely to affect water column stability, surface productivity, and global oxygen cycling in the northern Gulf of Mexico, which is the site of the largest (up to 16,500 km2) and most severe hypoxic zone (liter‒1) in the western Atlantic Ocean. We use a coupled physical-biological two-box model to investigate potential effects of climate change on seasonal oxygen cycling and hypoxia in river-dominated coastal waters. The model was developed and calibrated using comprehensive environmental data sets collected on the Mississippi River and in the northern Gulf of Mexico between 1985 and 1993. The relative magnitude of changes in river runoff and severity of hypoxia during the 1993 Mississippi River flooding provide an excellent data set for model verification. Model simulations for a doubled CO2 climate predict a 30–60% decrease in summertime subpycnoclinal oxygen content, relative to a 1985–1992 average. Under those conditions, the hypoxic zone in the northern Gulf of Mexico will expand and encompass an area greater than that of summer 1993.

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