Fouling caused by soluble microbial products (SMP) in membrane bioreactors (MBRs) is a critical problem, and a general understanding on SMP fouling behaviors has not been well established due to the complex interactions between SMP and membranes. In the present work, alginate solution was chosen as a model SMP foulant, and the effects of solution chemistry on the interaction energy between alginate and polymeric membranes were assessed by the extended Derjaguin–Landau–Verwey–Overbeek (XDLVO) theory. The results showed that the pH and ionic strength levels of the solution had significant effects on the solution properties and the interaction energy between alginate and membranes. The free energy of cohesion of alginate was maximal at pH 6.5 and ionic strength 10mM. Either increase or decrease of pH could lessen its cohesion free energy. Increase of ionic strength reduced the free energy of cohesion and made alginate solution more unstable and hydrophobic. Energy barrier between alginate and membranes was reduced under higher ionic strength and acidic condition, which was supported by fouling filtration experiments. It was also found that after the formation of initial fouling layer onto membranes, membrane fouling was controlled by cohesion free energy between approaching alginate and alginate-modified surfaces. This study demonstrated that XDLVO-model is sufficient to assess short-range membrane–foulant interactions and to predict SMP fouling in MBRs. Display omitted •We examine the interaction energy between membrane and alginate by the XDLVO theory.•High ionic strength and strong acidic condition can reduce interaction energy.•Cohesion free energy between alginate and virgin membrane governs initial fouling.•Interactions of foulant and foulant-modified surface dominate after initial fouling.•XDLVO-model can well characterize and predict biofouling behaviors.