Low oxygen conditions, often referred to as oxy- gen deficiency, occur regularly in the North Sea, a temperate European shelf sea. Stratification represents a major process regulating the seasonal dynamics of bottom oxygen, yet, low- est oxygen conditions in the North Sea do not occur in the regions of strongest stratification. This suggests that stratifi- cation is an important prerequisite for oxygen deficiency, but that the complex interaction between hydrodynamics and the biological processes drives its evolution. In this study we use the ecosystem model HAMSOM- ECOHAM to provide a general characterisation of the dif- ferent zones of the North Sea with respect to oxygen, and to quantify the impact of the different physical and biological factors driving the oxygen dynamics inside the entire sub- thermocline volume and directly above the bottom. With respect to oxygen dynamics, the North Sea can be subdivided into three different zones: (1) a highly produc- tive, non-stratified coastal zone, (2) a productive, season- ally stratified zone with a small sub-thermocline volume, and (3) a productive, seasonally stratified zone with a large sub- thermocline volume. Type 2 reveals the highest susceptibility to oxygen deficiency due to sufficiently long stratification pe- riods (textgreater60 days) accompanied by high surface productivity resulting in high biological consumption, and a small sub- thermocline volume implying both a small initial oxygen in- ventory and a strong influence of the biological consumption on the oxygen concentration. Year-to-year variations in the oxygen conditions are caused by variations in primary production, while spatial dif- ferences can be attributed to differences in stratification and water depth. The large sub-thermocline volume dominates the oxygen dynamics in the northern central and northern North Sea and makes this region insusceptible to oxygen de- ficiency. In the southern North Sea the strong tidal mixing inhibits the development of seasonal stratification which pro- tects this area from the evolution of low oxygen conditions. In contrast, the southern central North Sea is highly suscep- tible to low oxygen conditions (type 2). We furthermore show that benthic diagenetic processes represent the main oxygen consumers in the bottom layer, consistently accounting for more than 50% of the overall consumption. Thus, primary production followed by rem- ineralisation of organic matter under stratified conditions constitutes the main driver for the evolution of oxygen defi- ciency in the southern central North Sea. By providing these valuable insights, we show that ecosystem models can be a useful tool for the interpretation of observations and the es- timation of the impact of anthropogenic drivers on the North Sea oxygen conditions.