Description: An increasing number of dead zoning (hypoxia) has been reported as a consequence of declining levels of dissolved oxygen in coastal oceans all over the globe. Despite substantial efforts a quantitative description of hypoxia up to a level enabling reliable predictions has not been achieved yet for most regions of societal interest. This does also apply to Eckernförde Bight (EB) situated in the Baltic Sea, Germany. The aim of this study is to dissect underlying mechanisms of hypoxia in EB, to identify key sources of uncertainties, and to explore the potential of existing monitoring programs to predict hypoxia by developing and documenting a workflow that may be applicable to other regions facing similar challenges. Our main tool is an ultra-high spatially resolved general ocean circulation model based on a code framework of proven versatility in that it has been applied to various regional and even global simulations in the past. Our model configuration features a spacial horizontal resolution of 100 m (unprecedented in the underlying framework which is used in both global and regional applications) and includes an elementary representation of the biogeochemical dynamics of dissolved oxygen. In addition, we integrate artificial “clocks” that measure the residence time of the water in EB along with timescales of (surface) ventilation. Our approach relies on an ensemble of hindcast model simulations, covering the period from 2000 to 2018, designed to cover a range of poorly known model parameters for vertical background mixing (diffusivity) and local oxygen consumption within EB. Feed-forward artificial neural networks are used to identify predictors of hypoxia deep in EB based on data at a monitoring site at the entrance of EB. Our results consistently show that the dynamics of low (hypoxic) oxygen concentrations in bottom waters deep inside EB is, to first order, determined by the following antagonistic processes: (1) the inflow of low-oxygenated water from the Kiel Bight (KB) – especially from July to October – and (2) the local ventilation of bottom waters by local (within EB) subduction and vertical mixing. Biogeochemical processes that consume oxygen locally are apparently of minor importance for the development of hypoxic events. Reverse reasoning suggests that subduction and mixing processes in EB contribute, under certain environmental conditions, to the ventilation of the KB by exporting recently ventilated waters enriched in oxygen. A detailed analysis of the 2017 fish-kill incident highlights the interplay between westerly winds importing hypoxia from KB and ventilating easterly winds which subduct oxygenated water.