The aim of this paper was to determine the effect of two different membrane bioreactor (MBR) configurations (external/immersed) on sludge structure and microbial activity. Sludge structure was deduced from rheological measurements. The high shear stress induced by the recirculation pump in the external MBR was shown to result in decreasing viscosity due to activated sludge (AS) deflocculation. Besides, soluble microbial products (SMP) release was higher in the external MBR (5 mgCOD gMLVSS−1) than in the immersed configuration (2 mgCOD gMLVSS−1). Microbial activity was followed from respirometry tests by focusing on the distinction between heterotrophs and autotrophs. An easier autotrophic microbe development was then observed in the immersed MBR compared to the external one. However, the external MBR was shown to allow better heterotrophic microbe development.