Growth factors, such as vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF), and neurotrophic factors, including brain-derived neurotophic factor (BDNF), have attracted attention in studies of the biological effects of long-term stress exposure due to their neuroprotective roles. This study investigated whether circulating levels of EGF, VEGF and BDNF were altered in individuals with stress-related exhaustion disorder. Forty patients diagnosed with exhaustion disorder and 40 healthy subjects (50% women) provided fasting blood samples for analysis of EGF, VEGF, and BDNF in plasma. We found significantly lower levels of EGF, VEGF, and BDNF in patients with ED compared to healthy controls. This pattern was seen in both male and female patients. Given the important roles of BDNF and VEGF for brain plasticity and neurogenesis, decreased levels after long-term stress exposure could indicate increased risk of neuronal damage and cognitive impairments in this patient group.