Peliosis hepatis is a rare condition characterized by blackish-blue blood-filled cavities in hepatic parenchyma caused by dilatation of hepatic sinusoids. Peliosis hepatis has been described in secondary immunodeficiencies and certain medications. We present the first case of peliosis hepatis in a patient with a primary immunodeficiency, common variable immunodeficiency. A 44-year-old African-American male presented with gastrointestinal bleeding and elevated liver function tests. His medical history included common variable immunodeficiency and chronic kidney disease. The patient had jaundice, regenerative nodules on liver pathology, and low immunoglobulin levels. A magnetic resonance imaging of the abdomen with contrast revealed a cirrhotic liver, a 5 × 3 cm lesion, and poorly defined nodules which had decreased enhancement. A computed tomography-guided liver biopsy revealed peliosis hepatis, focal nodular hyperplasia, and fibrosis. No other etiology of his liver disease was found. The etiology of peliosis hepatis in patients with primary immunodeficiencies remains unclear. Additional studies are needed to understand the underlying mechanisms.