A two-stage submerged anaerobic membrane bioreactor (2-sAnMBR) was operated to demonstrate the technology concept and to accelerate anaerobic biodegradation of Palm Oil Mill Effluent (POME). Then, the impact of different high organic loading rates (OLR) was investigated with a focus on water quality and biogas production. OLR higher than 50 kgCOD.m-3.d-1 induced an increase of volatile fatty acids (VFAs). As a consequence, the biogas production decreased from 19.8 to 11.0 L.d-1 and CH4 yield between 0.23 to 0.38 LCH4/gCODremoved. Nevertheless, the highest OLR (98 kgCOD.m-3.d-1) made it possible to reach a COD removal effectiveness of 70%, where the membrane contribution was around 23.9% to 34.7%. The ratio of propionic acid/acetic acid appeared to be a key indicator to prevent the AnMBR operation failure. Indeed, as soon as the value of 0.7 has been exceeded, several signs of AnMBR failure appeared. The methanogenic activity in AnMBR was inhibited by a hydrolysis ratio of 13% which transformed to VFA accumulation in system. The 250 mg.L-1 of Phenol concentration in POME was an inhibitory of the microbe in this system. Suspended solids concentration, proteins, polysaccharides, and volatile fatty acids were the substantial parameters that influenced the fouling rate.