Work–family conflict is a phenomenon known to affect an individual’s well-being. However, its affective consequences are yet to be explored. In this study, we focus on understanding work–family conflict affective consequences on positive and negative affect. Our approach aims to refine the Job Demands and Resources model (JD-R model) by incorporating affect as a psychological mechanism in the health-impairment process and by exploring family-supportive organizational perceptions and psychological detachment as moderators. The final sample was composed of 195 couples, with men’s mean age around 46 years old (M = 46.85, SD = 0.34) and women’s age around 44 (M = 44.23, SD = 0.37). Men worked an average of 44.46 h per week (SD = 0.83), while women worked an average of 39.79 h per week (SD = 0.65). The majority of couples had full-time jobs (77.9% of men and 73.8% of women), worked fixed schedules (55.4% of men and 73.8% of women), were employed by others (75% of men and 82.8% of women), and worked for small companies (54.6% of men and 40% of women). Concerning education, most of the men (81.3%) and women (71.4%) attended high school or had less than 12 years of education. To test our moderation models, PROCESS version 4.1st macro for SPSS was used. Additional analyses included correlations and paired mean comparisons. Our findings indicate that work–family conflict correlates positively with negative affect and negatively with positive affect. Psychological detachment moderated the effect of work–family conflict on negative affect for women, but did not moderate the relationship with positive affect for men or women. Family-supportive organizational perceptions also did not moderate any of the proposed relationships. This study highlights how the ability to detach and separate family and professional domains is important and supports the health-impairment process of the Job Demands and Resources model through affective experiences.