Background: Saudi Arabia is considered the epicentre of MERS‐CoV. Since 2012, a total of 1844 cases of MERS‐CoV have been reported. A recent cluster, with 8 cases, has been reported in Najran region in the south‐western region of the country. This analysis of data from that region on health care workers (HCWs) awareness and attitudes towards the prevention and control of MERS‐CoV may be useful when planning health education programmes about this emerging infectious disease. Aims: We aimed to investigate the knowledge and attitude of HCWs toward MERS‐CoV in south‐western Saudi Arabia. Methods: This cross sectional study was conducted on HCWs in primary health care centres and hospitals at Najran. A questionnaire containing 14 knowledge and 8 attitude items was completed by all 870 participants. Results: Overall, > 80% of HCWs were aware about MERS‐CoV etiology, mode of transmission, risk factors, and signs and symptoms. Knowledge scores revealed 51% of participants had sufficient knowledge. Physicians and nurses had significantly better knowledge compared with other HCWs (p = 0.001). Participants who worked at institutions with established infection control programme scored significantly better on knowledge questions (P = 0.001). Concerning attitude, > 70% of HCWs exhibited a positive attitude toward MERS‐CoV. Conclusion: the HCWs in Najran region showed a high level of knowledge and positive attitude toward MERS‐CoV. There was a noticeable difference in knowledge level between different professions. Periodic educational interventions and professional campaigns are still needed. Any interventions should be directed towards the non‐physician and non‐nursing professions.