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Abstract. In late summer 2019 and 2020 bottom waters in southern Cape Cod Bay (CCB) became depleted of dissolved oxygen (DO), with documented benthicmortality in both years. Hypoxic conditions formed in relatively shallow water where the strong seasonal thermocline intersected the sea floor, bothlimiting vertical mixing and concentrating biological oxygen demand (BOD) over a very thin bottom boundary layer. In both 2019 and 2020, anomalouslyhigh sub-surface phytoplankton blooms were observed, and the biomass from these blooms provided the fuel to deplete sub-pycnocline waters of DO. Theincreased chlorophyll fluorescence was accompanied by a corresponding decrease in sub-pycnocline nutrients, suggesting that prior to 2019 physicalconditions were unfavorable for the utilization of these deep nutrients by the late-summer phytoplankton community. It is hypothesized thatsignificant alteration of physical conditions in CCB during late summer, which is the result of regional climate change, has favored the recentincrease in sub-surface phytoplankton production. These changes include rapidly warming waters and significant shifts in summer wind direction, bothof which impact the intensity and vertical distribution of thermal stratification and vertical mixing within the water column. These changes inwater column structure are not only more susceptible to hypoxia but also have significant implications for phytoplankton dynamics, potentiallyallowing for intense late-summer blooms of Karenia mikimotoi, a species new to the area. K. mikimotoi had not been detected in CCBor adjacent waters prior to 2017; however, increasing cell densities have been reported in subsequent years, consistent with a rapidly changingecosystem.