The influence of membrane fouling on the retention of four trace organic contaminants – namely sulfamethoxazole, ibuprofen, carbamazepine, and triclosan – by nanofiltration membranes was investigated in this study. Humic acid, alginate, bovine serum albumin, and silica colloids were selected as model foulants to simulate various organic fractions and colloidal matter that are found in secondary treated effluent and surface water. The effects of membrane fouling on the separation process was delineated by comparing retention values of clean and fouled membranes and relate them to the membrane properties (under both clean and fouled conditions) as well as physicochemical characteristics of the trace organic contaminants. Membrane fouling was dependent on the physicochemical properties of the model foulants. Initial foulant–membrane interaction could probably be a major factor governing the process of membrane fouling particularly by the organic foulants. Such membrane–foulant interaction was also a dominating factor governing the effects of membrane fouling on the membrane separation efficacy. In good agreement with our previous study (Nghiem and Hawkes, 2007 ), the effects of fouling on retention were found to be membrane pore size dependent. In addition, results reported here suggest that these effects could also be foulant dependent. It was probable that the influence of membrane fouling on trace organic retention could be governed by four distinctive mechanisms: modification of the membrane charge surface, pore blocking, cake enhanced concentration polarisation, and modification of the membrane hydrophobicity. The presence of the fouling layer could affect the retention behavior of charged solutes by altering the membrane surface charge density. While the effect of surface charge modification was clear for inorganic salts, it was less obvious for the negatively charged pharmaceutical species (sulfamethoxazole and ibuprofen) examined in this investigation, possibly due to the interference of the pore blocking mechanism. Evidence of the cake enhanced concentration polarisation effect was quite clear, particularly under colloidal fouling conditions. In addition, organic fouling could also interfere with the solute–membrane interaction, and therefore, exerted considerable influence on the separation process of the hydrophobic trace organic contaminant triclosan.