Autoimmune diseases such as idiopathic thrombocytopenic purpura and autoimmune hemolytic anemia have a high reported prevalence in patients with common variable immunodeficiency (CVID). We describe the case of a 36-year-old Hispanic man with CVID treated with intravenous immunoglobulin, who developed antineutrophilic cytoplasmic antibodies (ANCA)-associated vasculitis 15 years after immunodeficiency diagnosis. After failing first-line immunosuppressive therapy, the patient was successfully treated with rituximab. Although autoimmunity in the setting of CVID is well documented, this is the first report to describe a case of ANCA-associated vasculitis associated with CVID. Moreover, we report effective and safe use of rituximab in a patient with primary immunodeficiency.