This systematic review summarizes evidence about perceived stress in adults with epilepsy to clarify the particularities and potential effects on the prognosis and consequences of the disease. This review follows the recommendations of the PRISMA statement and was registered in PROSPERO. Thirty-four articles were selected. In 89% of the studies, stress in epilepsy was conceptualized as a process in which the demands of the environment exceed the organism's ability to cope. Stressful life events related to perceived stress in epilepsy included the COVID-19 pandemic and work-related problems. Perceived stress was identified as a seizure precipitant in 85% of studies. In 67% of studies, patients with epilepsy had higher perceived stress than healthy people. Female gender, youth, low educational levels, unemployment, poor social support, less than five years suffering the disorder, temporal lobe epilepsy, depression, poor seizure control, and polytherapy were identified as risk factors for increased stress. These studies highlight the need for the conceptualization of epilepsy within a chronic stress framework which could facilitate more appropriate clinical management.