The primary purpose of this study was to investigate the association between burnout and neural activation during working memory processing in patients with stress-related exhaustion. Additionally, we investigated the neural effects of cognitive training as part of stress rehabilitation. Fifty-five patients with clinical diagnosis of exhaustion disorder were administered the n-back task during fMRI scanning at baseline. Ten patients completed a 12-week cognitive training intervention, as an addition to stress rehabilitation. Eleven patients served as a treatment-as-usual control group. At baseline, burnout level was positively associated with neural activation in the rostral prefrontal cortex, the posterior parietal cortex and the striatum, primarily in the 2-back condition. Following stress rehabilitation, the striatal activity decreased as a function of improved levels of burnout. No significant association between burnout level and working memory performance was found, however, our findings indicate that frontostriatal neural responses related to working memory were modulated by burnout severity. We suggest that patients with high levels of burnout need to recruit additional cognitive resources to uphold task performance. Following cognitive training, increased neural activation was observed during 3-back in working memory-related regions, including the striatum, however, low sample size limits any firm conclusions.