Aim and objectives: To explore the experience of pulmonary exacerbation from the perspective of adults with cystic fibrosis. Background: While management of pulmonary exacerbations is a pillar of cystic fibrosis care, little is known of patients’ perspectives. Understanding the patient's experience is essential for developing and evaluating interventions in support of patient self-management. Design: Qualitative study with longitudinal study in a subsample. Methods: The study took place from 2015–2016 in a university hospital. Eighteen patients with cystic fibrosis were included who were ≥18 years of age and had no solid organ transplant. Patients’ experiences were explored through semistructured interviews and analysed using framework analysis. They each participated in one interview, with a subsample (N = 7) being interviewed twice during and once after antibiotic therapy. Results: Patients (11 men and 7 women; median age 29.5 years, range 19–55 years; median FEV1 45%, range FEV1 23%–105%) experienced pulmonary exacerbations as disruptions of their normality, which led to a substantial increase in their emotional distress. Exacerbations represented a period of threat and domination by CF; that is, symptoms and treatment consumed energy, restricted physical activity and daily life roles. “Noting change,” “waiting until antibiotics help,” “returning to normality” and “establishing a new normality” characterised their descriptions of the pulmonary exacerbation trajectory. Emotional distress was the major driver for patients’ self-management, and personal goals and illness beliefs influenced also patients’ self-management decisions. Conclusion: The experienced degree and source of emotional distress are drivers for self-management decisions in patients with cystic fibrosis who experience a pulmonary exacerbation. Relevance to clinical practice: Our data provide new understanding that will be essential to informing clinical practice, future patient-reported outcomes measures and intervention development.