Microbial colonization of implanted medical devices in humans can lead to device failure and life-threatening infections. One strategy to prevent this unwanted colonization is to coat devices with polymers that reduce bacterial attachment. This study investigates how mucins, a class of biopolymers found in mucus, can be used as surface coatings to prevent attachment of selected respiratory pathogens to polystyrene surfaces. Our data show that coatings of porcine gastric mucins or bovine submaxillary mucins reduce surface attachment by Streptococcus pneumoniae and Staphylococcus aureus, but not Pseudomonas aeruginosa. To elucidate how mucin coatings repel S. pneumoniae and S. aureus, the molecular components of mucins are examined. Our data suggest that mucin-bound glycans are key structural contributors of mucin coatings and are necessary for the repulsive effects toward S. pneumoniae and S. aureus.