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Background: Medical comorbidities are commonly encountered in chronic rhinosinusitis (CRS) and may impact both physical function and patient reported health-related quality-of-life (HRQOL). The functional comorbidity index (FCI) is designed to elucidate the role of comorbidities on functional prognosis. The objective of this study was to understand the impact of comorbidities known to impact physical function on baseline HRQOL using the FCI. Methodology: Patients meeting diagnostic criteria for CRS were prospectively enrolled in a cross-sectional study. Responses from the Sinonasal Outcomes Test-22 (SNOT-22), a measure of patient HRQOL, as well as the Lund-Kennedy and Lund-Mackay scores were recorded at enrollment. FCI was calculated retrospectively using the electronic medical record. Information was collected and compared for patients without (CRSsNP) and with nasal polyps (CRSwNP) using chi-square and t-tests. Spearman's correlations, followed by multivariate regression analysis, were used to assess the association between FCI and SNOT-22 scores. Results: One hundred and three patients met inclusion criteria for analysis. There were no significant differences in age, gender, and SNOT-22 scores between patients with CRSsNP and those with CRSwNP. FCI was significantly and independently associated with worse SNOT-22 scores (P =.012). FCI did not correlate with endoscopy and computed tomography scores. The mean FCI for patients with CRSsNP and CRSwNP was 2.02 and 2.24, respectively, and did not differ significantly between the two cohorts (P =.565). Conclusions: Major medical comorbidities known to affect physical function are associated with worse SNOT-22 scores in patients with CRS as measured by the FCI. [ABSTRACT FROM AUTHOR]