Background Patient positioning is an independent nursing intervention and may increase peripheral oxygenation for patients with lung disease. Few studies have been conducted on the effect of body positions on oxygenation in patients with lung disease. Aims and objectives To investigate the effects of five different positions on peripheral oxygen saturation (SpO(2)) and vital signs in patients with lung disease. Design A semi-experimental study was conducted. Methods Consecutive samples were recorded from critical care patients followed in the chest clinic of a university hospital. A total of 109 patients with lung disease were recruited. Patients who were able to lie in all positions, and who had unilateral or bilateral lung disease documented by a medical diagnosis by a physician were included in this study. The SpO(2) and vital signs were measured at each position three times. Results For patients with right, left, and bilateral lung disease, lying on the right side of the body at 45 in bed, the SpO(2) was higher, but this difference was not statistically significant. There was a significant difference at 40 minutes between the pulse rate in patients with left and bilateral lung disease, but not in patients with right lung disease. No significant differences were found between respiratory rates and body temperature in patients in any of the three groups at 10, 25, and 40 minutes. Conclusions Although this difference was not statistically significant, lying on the right side of the body at 45 in bed can be an effective position for improving oxygenation in all patients with lung disease. Relevance to Clinical Practice As there is insufficient evidence to suggest a specific position, further studies are needed. This study provides evidence that the best oxygenation in patients with unilateral and bilateral lung disease can be obtained by determining the appropriate position for critical care nurses.