Fatigue is an important symptom that negatively affects the quality of life of patients with many chronic diseases. Although it is reported to be one of the most impactful symptoms, fatigue is often overlooked or ignored by clinicians. The purpose of this study was to estimate the prevalence of fatigue and to determine its correlations with socio-demographic and health-related issues in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP). 138 CRSwNP patients and 102 healthy control subjects filled out the Multidimensional Fatigue Inventory (MFI), the Sino-Nasal Outcome Test-22 (SNOT-22), the Beck Depression Inventory (BDI) and the International Physical Activity Questionnaire (IPAQ). All subjects underwent a full ENT examination. Fatigue reportedly affected 53% of the patients with CRSwNP. A high percentage (37%) of patients with severe fatigue was noted. Among the three dimensions of fatigue which were assessed, physical fatigue was the most frequently reported. Patients with severe fatigue were significantly less physically active and had a greater symptom burden on the SNOT-22 (p < 0.05), but they did not differ in regard to the advancement of sinus disease. The BDI and SNOT-22 scores were also significant predictors of fatigue in CRSwNP patients (p < 0.001). Fatigue is common in patients with CRSwNP, with a particularly high percentage suffering from severe fatigue. Special attention should be paid to CRSwNP patients with higher SNOT-22 scores. [ABSTRACT FROM AUTHOR]