Abstract Background Living with a chronic disease, such as primary antibody deficiency, will often have consequences for quality of life. Previous quality-of-life studies in primary antibody deficiency patients have been limited to different treatment methods. We wanted to study how adults with primary antibody deficiencies manage their conditions and to identify factors that are conducive to coping, good quality of life and hope. Methods Questionnaires were sent to all patients ≥20 years of age with primary antibody deficiencies who were served by Rikshospitalet University Hospital. The questionnaires consisted of several standardized scales: Ferrans and Powers Quality of Life Index (QLI), Short Form-36 (SF-36), Jalowiec Coping Scale (JCS), Nowotny Hope Scale (NHS), and one scale we devised with questions about resources and pressures in the past. Of a total of 91, 55 patients (aged 23–76 years) answered the questionnaires. The questionnaire study were supplemented with selected interviews of ten extreme cases, five with low and five with high quality of life scores. Results Among the 55 patients, low quality of life scores were related to unemployment, infections in more than four organs, more than two additional diseases, or more than two specific occurrences of stress in the last 2–3 months. Persons with selective IgA deficiency had significantly higher QLI scores than those with other antibody deficiencies. An optimistic coping style was most frequent used, and hope values were moderately high. Based on the interviews, the patients could be divided into three groups: 1) low QLI scores, low hope values, and reduced coping, 2) low QLI scores, moderate hope values, and good coping, and 3) high QLI scores, moderate to strong hope values, and good coping. Coping was related to the patients' sense of closeness and competence. Conclusion Low quality of life scores in adults with primary antibody deficiencies were linked to unemployment and disease-related strains. Closeness and competence were preconditions for coping, quality of life and hope. The results are valuable in planning care for this patient group.