Introduction: The global prevalence of autoimmune diseases is about 5%. Patients with autoimmune conditions often report headaches. Headache has been reported to occur in patients with autoimmune disease, although its role as a direct symptom remains unclear. Differentiating whether the headache is related to autoimmune activity or represents a primary headache as a comorbidity is essential, as this distinction influences treatment strategies. The study aimed to describe the characteristics of patients with headache who have and do not have autoimmune disease. Methods: A cross-sectional study was conducted using secondary data from 1 January 2022 to 31 December 2022, with consecutive sampling. Bivariate analysis included the independent t-test, chi-square and Mann–Whitney tests. Results: Among 210 patients with headache, 22.4% had autoimmune diseases, mainly related to the connective tissue. The majority were females (77.6%) aged 18–45 years (50.5%). Over half of the patients with autoimmune diseases reported headaches after diagnosis, with a median onset of 4 years. The median headache frequency was 14 times per month, with a duration of 4 h and an intensity score of 5 on the numeric rating scale (NRS). Common triggers included fatigue (32.1%), while nausea and vomiting (66.7%) were more commonly reported as accompanying symptoms during headache attacks. Headache phenotypes varied between groups, with migraine more frequently reported in the autoimmune group (68.1%) and atypical presentations observed in 40.7% of patients with non-autoimmune disease. However, this may reflect referral patterns rather than true differences in underlying pathophysiology. Bivariate analysis showed significant relationships between age, gender, headache characteristics, onset and intensity with autoimmune status (p<0.05). Conclusion: The prevalence of patients with headache who have autoimmune disease was 22.4%. Significant associations were found between demographic and headache features and autoimmune status. © (2025), (Touch Medical Media). All rights reserved.