A sufficiently high oxygen supply is crucial for high-cell-density cultivation of aerobic microorganisms, including Schizochytrium sp. We, therefore, designed a novel bioreactor enabling high-level oxygen supply, and its relevant process parameters and fermentation-stage characteristics were investigated. The real-time changes of pH and nonoil biomass were monitored as proxies for the consumption of nitrogen and lipid accumulation status, which was first applied to divided fermentation process with three stages. The experimental results showed that the biomass in this porous-membrane-impeller bioreactor was higher than in conventional bioreactor, while docosahexaenoic acid (DHA) percentage in total lipids was lower than in conventional bioreactor. A multistage control strategy is subsequently implemented for the porous-membrane-impeller bioreactor, and the maximum biomass, DHA concentration, DHA percentage in biomass and DHA productivity reached 151.0 g/L, 44.3 g/L, 29.33%, 369.08 mg/(Lh), respectively. This study thus provides a highly efficient and economic bioreactor for the production of DHA by Schizochytrium sp. (c) 2017 American Institute of Chemical Engineers AIChE J, 63: 4278-4286, 2017