This study sheds light on the extent to which the five facets of mindfulness (observing, describing, acting with awareness, nonjudging, and nonreactivity), decentering, and reappraisal predict psychological distress via emotion regulation difficulties. The study sample is comprised of 620 undergraduate students (429 females and 191 males). The participants' ages range between 18 and 30 years (M-age = 21.88, SD = 1.68). Structural Equation Modeling (SEM) was employed to test the proposed model, which explained 57% of the total variance in psychological distress. According to the results, we conclude that decentering is indirectly associated with psychological distress, while neither a direct nor an indirect relationship was found between reappraisal and psychological distress. The various dimensions of mindfulness, describing, nonjudging, and nonreactivity, were indirectly related to psychological distress via emotion regulation difficulties. Both direct and indirect associations between acting with awareness and psychological distress were observed. These results reveal that decentering, describing, acting with awareness, nonreactivity, and nonjudging are significantly related to psychological distress through emotion regulation difficulties. Individuals who had higher decentering, acting with awareness, non-reactivity, and non-judging scores were less likely to report psychological distress, which was also associated with fewer emotion regulation difficulties. We discuss our results within the framework of the psychological distress literature and provide potential implications of these conclusions for future research and practice.