Clinical features of systemic lupus erythematosus (SLE) have been described from different geographical regions in the world. However, data from many Middle East countries, including Iran, are scarce. This study aims to demonstrate the demographic, clinical, and laboratory characteristics in Iranian patients with SLE. In this prospective study, all the patients referring to Shiraz educational hospitals (Nemazi-Hafez) with SLE (American College of Rheumatology criteria) during a 5-year period (2001 to 2006) were included. A complete history was taken; physical examination and routine hematological, serological, and immunological tests were done for each patient. There were 356 women and 54 men with an average age of 30.27 years at the onset of disease. Of the patients, 78% had hematological abnormalities, 65.5% had articular involvement, 54.5% had photosensitivity, and 60.5% had malar rash. Serositis occurred in 38% of patients of whom 12% had pericarditis and 26% had pleuritis. Nephritis was diagnosed in 48% of the cases and consisted always of glomerular nephritis. Biopsy-proven lupus nephritis was in most cases class IV(49.7% of all the biopsies). Oral ulcers were observed in 28% of patients. Neuropsychiatric manifestations, gastrointestinal involvement, and lymphadenopathy were observed in 31.5%, 8.3%, and 14.2% of patients, respectively. In all, 93% of patients were positive for antinuclear antibodies, whereas antidouble-stranded DNA was positive in 83% of patients. Coomb's positive hemolytic anemia appeared in 12.4% of the cases. Rheumatoid factor was detected in 9.7% of patients, and lupus erythematosus cell was seen in 32.5% of them. In all, 196 (47.8%) patients represented hypocomplementemia. Regarding hematological manifestations, 74.5% had microcytic hypochromic anemia, 64.6% had leukopenia, and 44.6% had thrombocytopenia; 18 (4.4%) patients died during the study period of which eight (2%) died because of cardiopulmonary involvement. Generally, there was more cutaneous, serositis, and neuropsychiatric involvement in our population than other Middle East countries. Serositis was associated with poorer prognosis, and the pattern of disease in these patients was much more sever than patients without serositis (P = 0.001). This is the first study of its kind in Iran. More multicenter studies should be undertaken in Iran to describe the pattern of SLE.