Background: The influence of the microbial community on inflammatory subtype in chronic rhinosinusitis (CRS) has been proposed. Superantigen mechanisms potentially create a T helper 2 (Th-2)/eosinophilic dominated inflammation as a product of local flora rather than an intrinsic mucosal process. The associations between culturable bacteria and the histopathology and clinical features of CRS patients are described. Methods: A cross-sectional study involving patients with CRS undergoing surgery was undertaken. Middle meatal swabs were performed at surgery for microbiological evaluation. Mucosal biopsies were taken and a blinded histopathological profile was performed. Disease specific quality of life and nasal symptom scores were recorded. The presence of culturable organisms and particular pathogens were compared with histopathology and clinical outcomes. Results: A total of 95 patients were assessed (48.4% female, mean age 45.6 ± 14.0 years), of which 47.3% had a culturable organism. Tissue eosinophilia (>10/high-power field [HPF]) was found in 46.1% of these patients and 30.3% had neutrophilic infiltrate, with the presence of neither Gram-positive organisms, Gram-negative organisms, nor species correlating to pathology subtype. A culturable pathogen was a predictor of subepithelial fibrosis (χ2 = 6.36, p = 0.04) and Gram-negative bacteria had the strongest association (χ2 = 18.82, p < 0.01). There were no other significant associations with other clinical outcomes. Conclusion: The culturable bacterial community has little impact on histopathology in CRS. While more sensitive tests may detect bacteria in the sinuses, the impact of the simple "culturable" bacteria on the underlying pathologic process is limited. Changes, such as subepithelial fibrosis, suggest colonization may lead to undesirable local mucosal damage and remodeling.