The operation of membrane bioreactors (MBRs) at high mixed liquor suspended solids (MLSS) concentrations (higher than 15 g L−1) may enhance the loading rate treatment capacity, while minimizing even further the MBR system’s footprint. However, oxygen transfer in wastewater treatment is significantly influenced by the MLSS concentrations. Particularly, conventional diffused aeration systems (fine and coarse bubble diffusers) exhibit a poor oxygen transfer in wastewater treatment applications; particularly, when operating at MLSS concentrations higher than 15 g L−1. The oxygen transfer performance of the supersaturated dissolved oxygen (SDOX) system was evaluated in activated sludge with MLSS concentrations from 4 to 40 g L−1 as a promising technology for uncapping such limitation. The operational conditions exerted by the SDOX technology did not affect the concentration of active biomass. Moreover, the biological performance of the MBR was not affected by the introduction of the SDOX technology. In addition, the microbial community was relatively stable although some variations at the family and genus level were evident during each of the study phases. Indeed, the membrane filtration performance was affected by the SDOX technology. A combination of several factors (certainly including particle size distribution of sludge) resulted in the serious membrane fouling imposed by the high-pressure and shear effects. However, this could be influenced due to the scale of the laboratory-based research. More research would be needed to confirm those findings.