Dissolved oxygen (DO) is an important parameter for evaluating the seawater quality of the oce-anic environment, but the distribution of DO and its possible mechanisms of marine environ-mental regulation are less studied. Here, the spatial distribution of DO and the influence of main environmental factors on DO were explored using in-situ observation data collected in the northern coastal waters of the Beibu Gulf in April 2021, based on cluster analysis, partial correla-tion analysis, and multiple linear regression. The results showed that DO in surface water of the study area gradually increased from nearshore to offshore, with the nearshore’s DO being nearly saturated and the offshore supersaturated. Tieshan Port and the Maowei Sea had the lowest degree of DO saturation. The partial correlation analysis between DO concentration and environmental factors revealed that the distribution of DO concentration was mainly influenced by temperature and salinity as well as other biochemical factors (i.e., chlorophyll-a, turbidity, and pH). Significant differences existed between the dominant factors in various parts of the northern Beibu Gulf. The western river (Beilun River, Fangcheng River, Maoling River, Qinjiang River) estuaries and offshore areas were dominated by photosynthesis, while the eastern river (Fengfeng River, Nanliu River) estuaries were dominated by oxidation-decomposition. In addition, DO was also affected by the mangrove ecosystem, aquaculture, and coastal industry.