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Background: The shortage of prevalence data based on a representative sample of the general population, as well as the small number of disorders covered in co-morbidity studies, are major issues in autoimmune disease research. In this study, the incidence of autoimmune illnesses in a representative sample of Saudi Arabia's general population is documented, and the hypothesis of an overall relationship between these diseases is explored. Methods: This was an analytical cross-sectional study to spot light on the prevalence of autoimmune disease among Saudi population. Since the aim of the study was to determine the prevalence of autoimmune disease and their relationship with chronic illnesses among Saudi, this is the suitable design for this research. The study was carried out among Saudi population. Data were collected from general population using questionnaire. Participants were chosen via probability simple random sampling technique. Participants were selected from the general population. The expected number of sample size was 700 participants. However, the study included 802 participants. Results: The study included the participation of 802 participants from both genders and different age groups in the Kingdom of Saudi Arabia. There were 436 female participants (54.4%) and 366 males (45.6%) took place in this study. The most prevalent age group was 45-54 years (n= 232, 28.9%). There were 199 participants reported having a family history of autoimmune diseases (24.8%). Furthermore, there were 186 participants who are using medications for high cholesterol level (23.2%) with no significant for gender (P= 0.08). Diabetes was prevalent among 203 participants (25.3%), blood pressure disorder (n= 211, 26.3%), ulcerative colitis (n= 137, 17.1%) and other comorbid conditions. Conclusion: In conclusion, this survey confirm relatively high prevalence of autoimmune disease among Saudi population. In addition, participants suffered from additionally comorbid conditions.