In recent years, oxygen deficit in coastal seas has seriously affected the marine ecological environment. Using a large number of observed data in May and August from 2015 to 2018, we obtain the vertical distribution of DO and related hydrological factors in the central section of the Bohai Sea by three-dimensional spatial interpolation to analyze the variation characteristics and its potential changing drivers. The results show that there are two typical oxygen deficit regions in the bottom water of the central Bohai Sea in summer, which are located off Qinhuangdao (QHD) and off the Yellow River estuary (YRE). We analyze the main mechanisms for the formation of oxygen deficit regions: continuous strong stratification and high temperature in summer as well as the aerobic decomposition of organic matter produced after the death of the massive phytoplankton in spring and summer during the slow sedimentation process. In addition, the physical-biological mechanisms of QHD and YRE, the two oxygen deficit core regions, are obviously different. This comparison highlights the influence of the initiation time of stratification enhancement and phytoplankton species on the degree of oxygen deficit, which provides a new understanding for perfecting the formation mechanism of oxygen deficit. Finally, two oxygen deficit regions are simply predicted, which highlights the seriousness of oxygen deficit in Bohai Sea.