Although mucus plays many different roles among marine invertebrates, relatively little is known about the link between biochemical structure and function. In the present study we focused on some physical and chemical properties of the polychaete Sabella spallanzanii's mucus such as viscosity, osmolarity, electrical conductivity, elemental composition, the protein and carbohydrate content, the total lipids and fatty acid composition, and polychlorinated biphenyls (PCBs) contamination. Moreover, an antimicrobial activity of the mucus was investigated. The water content of S. spallanzanii mucus was 96.2±0.3%. By dry weight 26±1.2% was protein, 8±0.21% was carbohydrate and only 0.1% lipid, much of the remainder of the dry weight was inorganic (about 65.2%). The estimated PCBs content was <0.005 μg g−1. The mucus of S. spallanzanii exerted a natural lysozyme-like activity and produced in vitro the growth inhibition of Vibrio anguillarum, Vibrio harveyi, Pseudomonas aeruginosa and Candida albicans. The findings from this study contribute to improve the limited knowledge available on the mucus composition in invertebrates and have implications for future investigations related to employment of S. spallanzanii mucus as a source of compounds of pharmaceutical and marine technological interest.