Banoub RG, et al. - Whether depressed mood would affect the link between chronic rhinosinusitis (CRS) symptom burden and decreased general health-related quality of life (QOL), was determined in this cross-sectional study. Participants were stratified as having well-controlled CRS symptoms [the 22-item Sinonasal Outcomes Test (SNOT-22)<35} and poorly-controlled CRS symptoms (SNOT-22≥35). SNOT-22 was used to measure CRS symptom burden and the EuroQol 5-dimensional health utility value (EQ-5D HUV) and visual analog scale (EQ-5D VAS) were used to measure general health-related QOL. Findings demonstrated a modulating impact of depressed mood on the link between CRS symptom burden and general health-related QOL. A threshold of CRS symptom burden or control was suggested, beyond which depressed mood—not CRS symptom burden—drives the association with general health-related QOL.