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Introduction: Systemic Lupus Erythematosus (SLE) is a chronic inflammatory disease of autoimmune origin that affects multiple systems, with the haematologic system being commonly involved. However, the co-existence of haemoglobinopathies and connective tissue disorders has rarely been investigated, and the available data on this matter are primarily anecdotal. Aim: To determine the prevalence of Haemoglobin E (HbE) haemoglobinopathy in adult SLE patients and to assess the association of HbE haemoglobinopathy and SLE with disease activity. Materials and Methods: A hospital-based cross-sectional study was conducted at the Department of General Medicine, Regional Institute of Medical Sciences (RIMS) Hospital, Imphal, Manipur, India, from April 2021 to July 2022. The study included SLE patients diagnosed during the study period who attended the rheumatology Outpatient Department (OPD). The independent variables were age, gender, occupation, religion, and family history, while HbE haemoglobinopathy, Mean Corpuscular Volume (MCV), Mean Corpuscular Haemoglobin (MCH), Red Blood Cell (RBC) count, and Systemic Lupus Activity Measure Revised Index (SLAM-R index) score were the dependent variables. Data were analysed using Statistical Package for Social Sciences (SPSS) version 21.0, with proportions analysed using the Chi-square test and Fisher’s-exact test, and means compared using Analysis of Variance (ANOVA) and independent t-test. A p-value of