Introduction. Lower extremity chronic venous disease (CVD) is a common cause of lower extremity pain and discomfort in the adult population of Western countries. The typical self-reported symptoms of CVD are aching, cramping, fatigue, heaviness, restlessness, and swelling. Physical activity is often evoked as a non-pharmacological and non-surgical intervention that can prevent venous disease progression and complications, as well as reduce symptoms and improve quality of life in CVD sufferers (1). Objectives. The aim of this study was to quantify fatigue and quality of life in CVD sufferers within a large cohort representative of the French population. Moreover, the link between physical activity and fatigue/quality of life of CVD sufferers was also further investigated. Methods. A survey was conducted on a representative sample of the adult French population, which comprised 3,008 subjects aged 18-93 years. All the procedures were approved by a local institutional ethics committee and performed in accordance with the Declaration of Helsinki (except for registration in a database). The venous symptoms were scored using a customized questionnaire to classify the participants into two groups: non-CVD subjects and CVD sufferers. Physical activity data were acquired using the Godin-Shephard Leisure-Time Physical Activity questionnaire (2). Fatigue was scored using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire (3). Quality of life scores of CVD subjects were acquired using the CIVIC-14 questionnaire (4). Stepwise procedures of selection of variables by using AIC and BIC criteria were performed. The beta coefficient (β) is the degree of change in the outcome variable for every one unit of change in the predictor variable. Results. In the French population, 32% of people were classified as CVD sufferers. Fatigue score was worst in CVD sufferers than in non-sufferers (35.0 ± 11.0 vs 40.4 ± 9.3, respectively; β = 5.49; 95% CI 4.73 to 6.24; p < 0.001). Within CVD sufferers, there was a relationship between fatigue score and quality of life score (β = 1.25; 95% CI 1.20 to 1.31; p < 0.001). Physical activity influenced the fatigue score in CVD sufferers (37.1 ± 10.4 vs 34.4 ± 11.1 in active and inactive, respectively; β = 3.38; 95% CI 1.68 to 5.82; p < 0.001). Physical activity affected the quality of life score in CVD sufferers (74.7 ± 20.1 vs 71.4 ± 21.5 in active and inactive, respectively; β = 3.90; 95% CI 0.56 to 7.26; p = 0.022). Conclusions. Fatigue, assessed using a validated questionnaire (i.e. FACIT-F), can significantly discriminate between CVD sufferers and non-sufferers. The fatigue score was also a good predictor of quality of life in CVD sufferers. Active CVD sufferers were less fatigued and their quality of life was less impacted. Therefore, physical activity might be considered as a treatment to alleviate CVD-induced symptoms of fatigue.