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The operation of membrane bioreactors (MBRs) at higher than usual mixed liquor suspended solids (MLSS) concentrations may enhance the loading rate treatment capacity while minimizing even further the system's footprint. This requires operating the MBR at the highest possible MLSS concentration and biomass activity (e.g., at high loading rates and low solid retention times (SRTs)). Both a negative effect of the MLSS concentrations and a positive effect of the SRT on the oxygen transfer have been reported when using conventional fine bubble diffusers. However, most of the evaluations have been carried out either at extremely high SRTs or at low MLSS concentrations eventually underestimating the effects of the MLSS concentration on the oxygen transfer. This research evaluated the current limitations imposed by fine bubble diffusers in the context of the high-loaded MBR (HL-MBR) (i.e., high MLSS and short SRT—the latter emulated by concentrating municipal sludge from a wastewater treatment plant (WWTP) operated at a short SRT of approximately 5 days). The high MLSS concentrations and the short SRT of the original municipal sludge induced a large fraction of mixed liquor volatile suspended solids (MLVSS) in the sludge, promoting a large amount of sludge flocs that eventually accumulated on the surface of the bubbles and reduced the free water content of the suspension. Moreover, the short SRTs at which the original municipal sludge was obtained eventually appear to have promoted the accumulation of surfactants in the sludge mixture. This combination exhibited a detrimental effect on the oxygen transfer. Fine bubble diffusers limit the maximum MLSS concentration for a HL-MBR at 30 g L−1; beyond that point is either not technically or not economically feasible to operate; an optimum MLSS concentration of 20 g L−1 is suggested to maximize the treatment capacity while minimizing the system's footprint. [ABSTRACT FROM AUTHOR]