In this study, the membrane autopsy was performed on a full-scale seawater reverse osmosis (SWRO) desalination plant located on the Red Sea. Several techniques were employed to characterize the nature and the fate of the foulants in the process, including LCOCD, ICP-MS, SEM-EDS, TSS, and ATP. The efficiency of the pretreatment in removing the fouling potential was assessed by analyzing the seawater after the intake feed pump, after the spruce media filter (SMF) and after the cartridge filter (CF). The autopsy of the membrane modules and CF operated for long-term revealed the presence of a heterogeneous fouling layer. The organic fraction composition of the fouling layer depended on the module position in the vessel. The inorganic deposits embedded in the layer were mainly composed of aluminum, iron, and magnesium silicate. The inorganic sediments entered the plants from the shoreline seawater intake and accumulated on the CF filter and the membrane. The analysis of the pretreatment performance showed an increase of TSS and ATP after CF, highlighting the inappropriate CF filter replacement time.