<p>Infertility is a disease with impact on the individuals’ lives which can be perceived as a stress-inducing experience. Higher levels of infertility-related stress have been associated with lower levels of quality of life. The aim of this study was to examine experiential avoidance as a pathway through which infertility-related stress is linked to quality of life in women with fertility problems. This cross-sectional study was conducted with a sample of 285 Portuguese women (<i>M</i> = 35.61; <i>SD</i> = 4.80) who completed a sociodemographic and clinical data sheet, and self-reported measures of infertility-related stress, experiential avoidance, and quality of life. The findings showed that infertility-related stress is positively associated with experiential avoidance and negatively associated with quality of life. Furthermore, experiential avoidance mediated the link between infertility-related stress and quality of life. Given that experiential avoidance may be a pathway leading to a worse adaptation, interventions focused on experiential avoidance may result in higher levels of quality of life in women dealing with fertility problems. Considering that this mechanism is a process underlying psychological inflexibility, which can be targeted by acceptance and commitment therapy, this therapy might be beneficial for women dealing with fertility problems, contributing to an improved quality of life. </p>