Chronic Norovirus infection is particularly challenging in patients with common variable immunodeficiency (CVID) because of their inability to achieve viral clearance and the risk of developing enteropathy leading to intestinal villous atrophy and malabsorption. To date, therapeutic options to eliminate the virus are limited and only ribavirin has been shown to induce viral clearance in norovirus enteropathy associated with CVID. We report a case of a 48-year-old female patient diagnosed with CVID enteropathy possibly related to norovirus infection who failed a ribavirin-based therapy despite dosage optimization through drug plasma level monitoring.