Membrane modules for seawater desalination are becoming increasingly important for obtaining clean water with the rising global water scarcity. The productivity of membrane modules is compromised by biofouling on the membrane and feed spacer. Biofouling development can be mitigated by modification of the spacer or membrane surface. The purpose of the present study is to evaluate the impact of surface-modified feed spacers on the cleaning performance of spiral-wound membrane filtration systems. After cold-plasma treatment, the feed spacers were modified with various combinations of polydopamine (PDA) and silver nanoparticles (AgNP). To compare the cleaning performance of the modified and unmodified spacers, membrane fouling simulators containing nanofiltration membranes and feed spacers were tested under industrially representative conditions: two full cycles involving biofilm development followed by cleaning-in-place (CIP). The modified spacers significantly improved the CIP efficiency when compared with that of the unmodified feed spacer. The highest CIP efficiency was obtained for the PDA–AgNP-coated spacers, which removed >90 % of the biomass. The PDA layers remained undetached during the CIP process, and the amounts of AgNP decreased without affecting the CIP effectiveness during consecutive operational cycles. The results demonstrate that CIP should be included in biofouling tests to evaluate the full potential of surface modifications and suggest that hydrophilic and biocidal spacer surface coatings can significantly improve the CIP effectiveness, thereby considerably reducing the CIP frequency and operational costs.