Résumé : Background: This study aims to examine the combined role of work and domestic burden on women’s and men’s perceived well-being. Methods: Observations result from two large Belgian cohorts [SOMSTRESS (1999-2002) and BELSTRESS III (2004-2008)] comprising 4810 workers in 9 firms, aged between 28 and 66. Three logistic regressions were performed using respectively (1) anxiety (SLC-90), (2) chronic fatigue (Vercoulen), and (3) subjective health evaluation as dependent variables. Sex, occupational stress (“iso-strain”, Karasek), and home-work interference (Kelloway) were entered as independent variables. Adjustments were made for age, education, occupation, social support outside work, child(ren) responsibilities, and marital status. Findings: High iso-strain, high home-work interference and their interaction are predictive of anxiety and chronic fatigue, especially in women. Bad health evaluation is linked to high iso-strain and high home-work interference but no sex effect was found. Discussion: findings will be discussed within the frame of the gender roles perspective.