<b><i>Background:</i></b> Multimorbidity can be operationalized as the presence of multiple psychosomatic symptoms and has been shown to be detrimental to the quality of life across the life span. Middle-aged adults are generally engaged in multiple life domains simultaneously. This is one of the developmental challenges of middle adulthood as it can lead to conflict between the demands of different domains and, in turn, contribute to multiple psychosomatic symptoms, thereby diminishing the quality of life. This may be particularly true for women. Facilitation between life domains may serve to reduce the number of psychosomatic symptoms. However, this subject has been largely neglected in the literature. <b><i>Objective:</i></b> We aimed to close this gap by investigating the influence of conflict and facilitation between life domains (work, family, leisure) on self-reported psychosomatic symptoms in middle-aged women and men. <b><i>Methods:</i></b> Life domain conflict/facilitation and psychosomatic symptoms were assessed via self-report in a cross-sectional study with 277 adults aged 30-55 years (mean = 41.70, SD = 7.2; 56.7% women) who all worked at least 30 h/week and lived with their partner or family. <b><i>Results:</i></b> In line with our hypothesis, women reported more psychosomatic symptoms when they experienced conflict between life domains. However, contrary to expectation, they did not profit more from facilitation than men and, at low levels of facilitation, women even reported more psychosomatic symptoms than men. In men, there was no association between life domain conflict/facilitation and psychosomatic symptoms. The results were robust when statistically controlling for neuroticism. <b><i>Conclusions:</i></b> Engagement in multiple life domains influences the frequency of psychosomatic symptoms in women, but not in men: women suffer more and profit less than men from combining work, family and leisure.