It has long been recognized that environmental influences play an important role in the risk of developing Autoimmune disease. Defining specific pathogenic environmental mediators that may trigger the development or progression of autoimmune disease remains a focus of increasing investigative effort. Factors promoting disease may not be identical to factors that influence the severity or progression of the disorder. The cause(s) of autoimmune disorders remain largely unknown. Considerable evidence supports a role for environmental agents in inducing autoimmune disorders. OBJECTIVES: The study aims to explore the risk factors of autoimmune diseases among attendants of general hospitals in Aseer Region. Methods: case control study design was carried out included 70 patients with multiple types of auto immune diseases attending general hospitals and primary health care centers in Abha city. They were clinically diagnosed as having autoimmune diseases. and 140 clinically free subjects , age and sex matched were included as controls. RESULTS: The present study included 70 autoimmune disease patients predominantly females (88.4%). Their mean age was 42.7 ± 12.1 years and disease duration was 11.2 ± 7.2 years. The mean age of the control group was 47.1 ± 13.6 years with no significant differences in the demographic data between the patients and control (p > 0.05). This study found no significant differences between cases with autoimmune diseases and sociodemographic characteristics. Conclusion :There is multiple determinants and risk factors affecting the occurrence of autoimmune diseases. Familial history, psychological stresses, hormonal supplementation, using hair dyes, smoking and recent vaccination were significant factors associated with autoimmune diseases.