Aims: To study the histomorphology of duodenitis associated with systemic autoimmune diseases with clinicopathologic correlation. Patients and Methods: This is a descriptive prospective study. Fifteen patients of autoimmune diseases with duodenitis were included. Informed consent was taken. Histomorphological parameters studied were villous architecture, crypt architecture, intraepithelial lymphocyte (IEL) count per 100 enterocytes, villous tip IEL count per 20 enterocytes were counted, inflammatory cells in lamina propria—lymphocytes, neutrophils, eosinophils, epithelioid cells. Statistical analysis was done using IBM-SPSS software version 21. Results: Fifteen cases of duodenitis associated with autoimmune diseases included 6 patients of systemic lupus erythematosus (SLE), 5 of rheumatoid arthritis, one each of ankylosing spondylitis, systemic sclerosis, dermatomyositis and seronegative reactive arthritis. All these cases were serologically proven. Only 3 (20%) patients had mild villous blunting. Six patients (46.7%) had increased IEL counts. The range of IELs was 8 - 30, mean ± SD was 14 ± 7.6. Range of villous tip IELs was 0 - 8 with mean ± SD of 3.45 ± 2.56. Six patients (46.7%) had increased IEL counts but only 3 patients (20%) had increased villous tip IELs. All patients had moderate increase in lymphoplasmacytic infiltrate in lamina propria. Eosinophils in lamina propria were increased in 46.7% cases.? Conclusion: One of the causes for malabsorptive conditions in adult population in South India is found to be duodenitis associated with autoimmune conditions. We conclude that a combination of clinical, serological, endoscopic and histopathologic features is crucial in arriving at a correct diagnosis.