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Purpose To quantify the health related quality of life in primary immunodeficiency patients. Materials and methods We used generic health status and general psychological health questionnaires to determine the range of issues that needed to be considered in examining the burden of common variable immunodeficiency (CVID). Results The health status of patients with CVID was lower than that observed in normal subjects. Overall, Role-Physical and General Health scales correlated with a poorer clinical status. Surprisingly, the duration of disease did not influence health status. Being female, older, General Health Questionnaire-positive and alexithymic proved to be major risk factors associated with a poor health status. Patients with chronic lung disease and chronic diarrhea had the lowest values on the Medical Outcome Study, Short Form SF-36 (SF-36) scales. Disease severity perception was associated with the General Health Questionnaire and alexithymia status. Limitations in daily activities as a result of lower physical health were the major problems facing common variable immunodeficiency patients. Conclusion Our data underlined the importance of conducting a periodical health related quality of life assessment on patients with primary antibody deficiencies and, moreover, stressed the necessity of providing psychological support to at risk patients.