The aim of this study is to examine the mediator role of the cognitive flexibility and mindfulness in the relationship between perceived stress and distress tolerance in university students. The sample of the study consisted of 417 students (306 females: 73,4%, 111 males: 26,6%) at Faculty of Healthy Sciences in Istanbul Medeniyet University in Turkey. Sample’s mean of age came to 19,88 (Sd=1.93). The Perceived Stress Scale, Distress Tolerance Scale, Cognitive Flexibility Scale, and Mindfulness Scale have been used. As part of this study, the mediating role of cognitive flexibility and mindfulness in the relationship between perceived stress and distress tolerance has been tested using the Serial Mediator Model. The results have indicated that those with a higher level of perceived stress experience lower degrees of cognitive flexibility and that, given cognitively less flexible individuals experience less mindfulness, thus, lower levels of mindfulness are associated with a decrease in distress tolerance. Moreover, the model in its entirety proved statistically significant (F(3, 420)=33.87, p<.001), accounting for 19,4% of the total variance. The findings have been discussed in line with relevant literature on the issue and recommendations on their possible application have been given.