Background: Systemic lupus erythematosus (SLE) is a potentially severe, frequently disabling autoimmune disease with multi-organ involvement. Although SLE has the potential to affect any organ, the lungs are commonly involved.Objectives: To study and analyze the prevalence, clinical features, and prognosis of pleuro-pulmonary involvement in patients with systemic lupus erythematosus (SLE).Patients and Methods: We reviewed the medical records of all SLE patients (402) who were admitted in the Rheumatology and Rehabilitation in patient department, Faculty of Medicine, Cairo University from 2000 to 2013.Results: In the 402 SLE patients pleuro-pulmonary system affection occurred in 265 patients being the 3rd most common affected system after musculo-skeletal and haematological systems. Pleurisy was the most common clinical finding occurring in 163 cases (61.5%) while the pleural effusion occurred in 65 cases (24.5%).Pulmonary infection was the second most common pleuro-pulmonary manifestation affecting 153 cases (57.7%).Pulmonary manifestations less commonly present were pulmonary hypertension occurring in 22 cases (8.3%), interstitial lung fibrosis occurred in 11 cases (4.2 ), pneumonitis (5 cases, 1.9%), bronchiolitis (3 cases, 1.1%), clinical shrunken lung syndrome and alveolar hemorrhage (each one occurred in 2 cases, 0.8%) and finally 1 case (0.4%) was suffering from bronchiactasis and another one from acute pulmonary oedema. The most common clinical symptoms were pleuritic chest pain occurring in 135 cases (50.9%), cough (productive or dry) in 130 cases (49.1%).The most common auto-antibodies were ANA which was presented in 251 cases (94.7%) and Anti-DNA in 159/183 cases (86.8%).A significant correlation was found between pulmonary affection and CNS lupus, positive ANA and the number of drug intake (p= 0.01, 0.002 and 0.003 respectively). We found a highly significant correlation between both pleural and pulmonary systems affection and the X-ray findings (p< 0.0001 and p= 0.032).A highly significant correlation was found between the presence of pleural effusion and pericardial effusion in SLE patients (p=0.001). And finally, there was a significant correlation between the presence of chest infection and the presence of other non pleuro-pulmonary infections throughout the patient disease course (P=0.034).Conclusion: The pleuro-pulmonary system is one of the most commonly affected systems in SLE. Pleurisy was the most common clinical finding followed by pulmonary infection and pleural effusion.