Introduction: Acute acalculous cholecystitis (AAC) involves inflammation of the gallbladder without the presence of gallstones, and is commonly seen in ill hospitalized patients. We present a case of acalculous cholecystitis as the initial presentation of systemic lupus erythematosus (SLE). Case Description/Methods: A 34-year-old woman presented with two weeks of fever, epigastric pain with nausea, and a 10-pound weight loss. Review of systems was positive for dry eyes, dry mouth, and myalgias. Past medical history was notable for miscarriage. Complete blood count was notable for thrombocytopenia, normocytic anemia, and neutropenia (with absolute neutrophil count of 660 10*3/uL). Comprehensive metabolic panel was notable for an elevated protein gap and slightly abnormal AST 161 IU/L and ALT 61 IU/L. CT abdomen demonstrated gallbladder wall thickening, with no evidence of cholelithiasis. RUQ ultrasound confirmed the absence of gallstones. HIDA scan showed non-visualization of the gallbladder consistent with cystic duct obstruction. Erythrocyte sedimentation rate was elevated at 56 mm/hr and ferritin was greater than 4000 ng/ml. Further testing revealed positive testing for ANA, double-stranded DNA, anti-ro, and lupus anticoagulant. Given the predominant autoimmune symptoms, she was started on prednisone 60 mg for newly diagnosed lupus with improvement of her symptoms. After discharge she was started on plaquenil and azathioprine, and steroids were tapered. Repeat testing confirmed persistent antibodies for antiphospholipid syndrome. She was lost to follow up 6 months after discharge. Discussion: GI manifestations of lupus can be vast, and include oral ulcers, mesenteric vasculitis, intestinal pseudo-obstruction, protein losing enteropathy, lupus associated pancreatitis, and serositis. Hepatobiliary manifestations include primary sclerosing cholangitis and autoimmune cholecystitis. The pathogenesis of AAC in SLE typically involves vasculitis, serositis, or thrombosis, and gallbladder histology often shows vasculitis of small vessel arteries and venules. Treatment typically involves percutaneous cholecystostomy tube placement or cholecystectomy; however, there have been case reports of successful treatment of AAC in SLE with high dose corticosteroids, often in combination with antibiotics or other immunosuppressants. Our case demonstrates the importance of considering underlying autoimmune conditions in patients presenting with gastrointestinal symptoms.