The first serial mediation analysis was used to investigate the role of HPA activation in stress-related changes in creativity and cognitive performance. This model was tested with Group (stress group or control group) as the independent variable, the cortisol AUCi (T1 to T6) as the first mediating variable, the changes in cognitive flexibility performance (the post-WCST score minus pre-WCST score) as the second mediating variable and the variations of creative task performance (changes in fluency, flexibility, and originality of the AUT) between pre-test and post-test (post-test score minus pretest score) as dependent variables. The results supported a serial mediation model (see Figure 6): stress condition was associated with higher HPA activation, which reduced cognitive flexibility, leading to worse creativity performance (parameter a1 × d × b2 = 0.296, [0.029, 0.897]).