Comprehensive fouling propensity associated with the change of soluble microbial products (SMP), especially the concentration of SMP and the ratio of protein to polysaccharide (PN/PS) has been investigated in a lab-scale submerged microfiltration MBR. Results showed that the higher ratio of PN/PS induced less irreversible fouling and improved the interaction of protein and polysaccharide to form cake layer. The rejection efficiency of major components in SMP also increased with higher PN/PS ratios. Fouling mechanisms altered from combination of intermediate pore blocking and cake formation at initial stage to cake formation on the membrane surface during long-term operation. Moreover, the irreversible fouling resistance was found to be proportional to the concentration of SMP. Lower concentration of SMP and higher PN/PS ratio should be an effective strategy in releasing membrane fouling.