Emergency departments in hospitals are environments characterized by high levels of stress, presenting significant physical and emotional demands for the professionals employed. The staff could be exposed to various forms of burnout and should be highly efficient with traits of resiliency to cope with such stress. Burnout syndrome (BOS) is characterized by high levels of emotional exhaustion, a sense of depersonalization and a feeling of lack of personal achievement. The objective of the study was to find the prevalence of BOS and the coping mechanisms among emergency department staff at different hospitals of Jazan region in Saudi Arabia. A cross-sectional study was conducted using Maslach Burnout Inventory scale, a widely adopted tool for measuring burnout, to collect data from eight hospitals in Jazan. The modified Brief Coping Orientation to Problems Experienced (COPE) inventory was used to assess the coping mechanisms. Emergency department professionals including medical, nursing, administrative and paramedic staff were studied. Prevalence was calculated and multiregression analysis was performed. BOS, with all the three characteristics, was prevalent among only 7 members (3.5%), with higher scores of emotional exhaustion and depersonalization among 40 (20%) and 125 (62.5%) respectively and low scores of personal accomplishments among 38 (19%). The highest coping mechanism adopted was religious coping, which was common among 92 members of staff (46%). The study found a low overall prevalence of the BOS among the emergency department staff. It was relatively higher among nurses, and the most used coping mechanism was religious coping. The higher depersonalization scores should be investigated further and addressed accordingly.