Systemic Lupus Erythematosus (SLE) is a multifaceted autoimmune disorder characterized by diverse clinical manifestations, including a significant prevalence of headaches. This cross-sectional study aimed to thoroughly explore the relationship between SLE and headaches by analysing their prevalence, types, and associated clinical, immunological, and radiological factors. A comparative analysis was conducted on 179 SLE patients, who were categorized into two groups: those with headaches and those without. Data collection encompassed demographic details, disease activity levels, neurological assessments, immunological profiles, and brain imaging results. Headaches were diagnosed and classified following the International Classification of Headache Disorders (ICHD-3). Disease activity was measured using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Statistical analyses were performed to identify significant associations and correlations. Headaches were observed in 55% of the SLE patients, predominantly presenting as tension-type headaches (65%) and migraines (27%). Notably, no patients met the criteria for a lupus-specific headache. The Headache Group exhibited significantly higher disease activity (SLEDAI scores). Tension-type and migraine headaches were particularly associated with increased muco-cutaneous manifestations. The presence of antiphospholipid (aPL) antibodies was significantly linked to migraines and cluster headaches. While neurological disorders such as ischemic stroke and venous sinus thrombosis were more prevalent in the Headache Group, these findings were not statistically significant. Brain MRI abnormalities were detected in 9.4% of patients with headaches, including venous sinus thrombosis (2.3%), ischemic stroke (5.8%), and white matter hyperintensities (1.1%). This study underscore es the complex relationship between SLE and headaches, suggesting that headaches may serve as an indicator of heightened SLE disease activity. Immunological factors, particularly aPL antibodies, show a strong association with specific headache types. MRI abnormalities further emphasize the intricate neurobiological aspects in SLE patients experiencing headaches. Continued research is essential to better understand biomarkers, genetic factors, and effective treatment strategies for managing headaches in SLE patients.