Background: Increasingly bacterial biofilms have been implicated in chronic rhinosinusitis (CRS), and conventional treatment methods have failed to completely eradicate biofilms. (1) Terminal sialic acids present on sinus mucosal glycoproteins are targets for bacterial adherence and biofilm formation. (2) A subpopulation of CRS patients is more susceptible to biofilm formation due to aberrant terminal sialic residue distribution patterns of glycoproteins on their mucosa. (3) The higher levels of sialyl transferase (ST)6Gal1 gene expression contribute to the overall aberrant glycosylation patterns on the host mucosa that predispose this patient cohort to developing biofilms. (4) Mucin glycoprotein MUC7 that has known bactericidal activity displays an overall reduced terminal sugar profile in biofilm positive CRS patients. Methods: Confocal scanning laser microscopy, glycoarray analysis, real-time polymerase chain reaction of ST6Gal1, neuraminidase assays and multivariate analysis were used to compare production of sialic acid - degrading enzymes in sinus biopsies from biofilm positive and negative CRS patients with mucosa from healthy controls. Results: Biofilm-positive CRS patients expressed aberrant glycoprotein patterns with terminal sialics of between 70 and 90 kD (stress value = 0.1414). The ST6Gal1 gene was upregulated, and bacteria isolated from these patients exhibit significantly higher neuraminidase activity (p = 0.0343). We detected a significant lack in the overall expression of terminal sugar residues of MUC7 (stress value = 0.088). Conclusions: We observed a strong positive correlation between the aberrant terminal sugar patterns in this sub group of CRS patients with biofilms. The innate immunity function of their MUC7 glycoprotein against bacterial invasion may be compromised in CRS patients.