The small intestine, which includes the duodenum, jejunum, and ileum, can be affected in rheumatologic and vasculitic conditions. In assessment of patients with rheumatic disease and gastrointestinal tract symptomatology, an understanding of normal small intestine physiology as well as the mechanism of immune dysfunction is critical. Careful patient assessment and proper use of diagnostics is mandatory for systemic lupus erythematosus (SLE), sarcoidosis, polyarteritis nodosum (PAN) and other forms of mesenteric vasculitis, Degos, and systemic sclerosis (SSc) with possible small bowel symptoms. Complications of altered physiology, such as malnutrition, small intestinal bacterial overgrowth (SIBO), pseudo-obstruction, impaired motility, arteriovenous malformation (AVM) and bowel perforation can occur in these diseases. Exclusion of mimics of rheumatologic disease is similarly important when assessing a patient with possible small bowel disease.