Purpose: Gastrointestinal (GI) involvement in SLE is not uncommon. However, SLE is often overlooked in the differential diagnosis of patients who present with certain GI symptoms. We describe a case of chronic diarrhea as the predominant presenting feature of SLE. Methods: N/A Results: A 63 year-old African American lady was admitted repeatedly to the hospital with nausea, vomiting and diarrhea over 5 months. She had no arhralgias or swelling. The patient appeared cachectic with satisfactory vitals, conjuncivae were pale, and FOBT was (+). Labs showed a hemoglobin 8 g/dl, BUN 40 mg/dl, creatinine 3.1 mg/dl, magnesium 1.3 mg/dl and potassium 2.7 mmol/l. Urine analysis showed hematuria, pyuria and nephrotic range proteinuria. Further investigations revealed iron, folate and vitamin D deficiency. Stools had no pathogens or parasites. Poor tolerance of a 100 g/day fat diet precluded 72-hour fecal fat test. Kidney ultrasound disclosed hydronephrosis without stones. An upper endoscopy and colonoscopy demonstrated ulcerative esophagitis with esophageal and gastric stasis. Small bowel and colon biopsies were unremarkable including a Congo red stain. Her hydronephrosis and obstructive uropathy required bilateral ureteral stent placement and an indwelling Foley catheter. Her diarrhea was treated with cholestyramine and electrolyte replacement without success. Because of the multi-organ involvement, further investigations for paraproteinemia and autoimmune disease were undertaken. Serologic studies revealed a positive ANA and a positive anti-dsDNA and anti-Smith antibodies. Her anemia, proteinuria and the positive antibodies were all consistent with the diagnosis of systemic lupus erythematosus. Therapy with corticosteroids was started, with an excellent response; the diarrhea subsided within 48 hours, and the patient regained weight and strength. Conclusion: Gastrointestinal symptoms account for 25–40% of the presenting clinical manifestations of SLE. It can affect the entire GI tract. However, GI symptoms as the sole presentation of SLE are a rare phenomenon. Chronic diarrhea in SLE can be secondary to colitis, celiac disease, protein losing enteropathy, or malabsorption. Interestingly, the random gastrointestinal biopsies in our patient did not show any significant pathological abnormalities. We hypothesize that our patient may have had either patchy small bowel disease or possibly malabsorbtion from dysmotility. Moreover, there are a few reports in the literature on the association of obstructive uropathy and intestinal malabsorption in SLE patients. This case highlights chronic diarrhea with obstructive uropathy as a possible, albeit unusual, presentation of SLE.