Hypoxia and oxygen deficient zones are expanding worldwide. To properly manage this deterioration of the marine environment, it is important to identify the causes of oxygen declines and the influence of anthropogenic activities. Here, we provide a study aiming to explain the declining oxygen levels in the deep waters of the Bothnian Sea over the past 20 years by investigating data from environmental monitoring programmes. The observed decline in oxygen concentrations in deep waters was found to be primarily a consequence of water temperature increase and partly caused by an increase in dissolved organic carbon (DOC) in the seawater (R-Adj(2). = 0.83) as well as inflow from the adjacent sea basin. As none of the tested eutrophication-related predictors were significant according to a stepwise multiple regression, a regional increase in nutrient inputs to the area is unlikely to explain a significant portion of the oxygen decline. Based on the findings of this study, preventing the development of anoxia in the deep water of the Bothnian Sea is dependent on the large-scale measures taken to reduce climate change. In addition, the reduction of the nutrient load to the Baltic Proper is required to counteract the development of hypoxic and phosphate-rich water in the Baltic Proper, which can form deep water in the Bothnian Sea. The relative importance of these sources to oxygen consumption is difficult to determine from the available data, but the results clearly demonstrate the importance of climate related factors such as temperature, DOC and inflow from adjacent basins for the oxygen status of the sea.