Background: Breathlessness, along with the associated inability to engage in normal activity, is one of the most distressing symptoms for patients with chronic obstructive pulmonary disease (COPD).Aim of study: The aim of this study was to evaluate the effect of nursing intervention program on patient knowledge and practice regarding breathlessness in patients with chronic obstructive pulmonary disease. Subjects and Methods: Research design: A quasi experimental research design was used. Setting: The study was conducted in chest department at Aswan University Hospitals. Subjects: Convenient sample of40 adult patients with COPD were recruited for the purpose of the study. Tools of data collection: Questionnaire form about Patient Knowledge, Patients' Practices Observational Checklists, Modified Borg Scale (MBS), Hospital Anxiety and Depression Scale (HADS) and Rotterdam Symptoms Checklist were used to collect data. Results: All of the studied patients had unsatisfactory knowledge and practices regarding COPD and breathlessness before nursing intervention program, which improved after program intervention with highly significant differences. Also, the breathlessness, anxiety and depression and dimensions of Rotterdam symptoms checklist improved significantly in patients with COPD who received nursing intervention program. Conclusion: Implementation of nursing intervention program had statistically significant improvement in patients' level of knowledge, practices, dyspnea, anxiety, depression level and dimensions of Rotterdam symptoms checklist. Recommendations: Conducting comprehensive health education programs for patients with COPD in outpatients' clinics with simplified printed guidelines through leaflets or brochures explaining how to prevent and control breathlessness and further evaluation of the effect of strategies to prevent and ameliorate breathlessness intensity and distress responses in larger sample of COPD patients in order to generalize the results.