Therapeutic plasma exchange (TPE) is a procedure performed on patients suffering from various disorders, including thrombotic thrombocytopenic purpura (TTP). As we noted a frequent transient deterioration in respiratory function when the procedure was performed on intensive care unit (ICU) patients, we studied retrospectively the incidence of respiratory deterioration during and shortly after TPE and looked for a probable correlation with a change in the white blood cell (WBC) counts. Over a period of 10 months six patients with TTP, five of whom had parenchymal lung disease due to different medical reasons, underwent TPE. The oxygen saturation was measured continuously before, during, and after TPE; additionally, the WBC and differential counts were measured pre-and post-TPE. The ratio of the oxygen saturation by pulse oxymetry (SpO 2 ) to the fraction of inspired oxygen (FiO 2 ) was calculated before, during and after TPE. In these five patients with lung disorders, there was a consistent trend of a decreasing SpO 2 /FiO 2 quotient during and within 2 h post TPE compared to the pre-TPE value. The decrease in SpO 2 /FiO 2 range was 0.20-0.89 with an average of 0.56. In the same 5 patients there was an increase in the WBC count in the range of 2.3-19.7 Γ 10 9 /L with an average increase of 9.3 Γ 10 9 /L. The percent neutrophils of the total WBC counts also increased following most of the sessions, this increase was in the range of 1-15 % with an average of 7%. The effect of TPE on the SpO 2 /FiO 2 ratio and the correlation to the WBC count and to a possible neutrophil activation has not been previously reported. We postulate that TPE can accentuate respiratory deterioration in patients with TTP who already have acute lung injury. This may be due to the priming and activation of the leukocytes that could lead to the release of cytokines and inflammatory mediators during the procedure. Thus, it is important to be aware of the possible deterioration in respiratory function and gas exchange while administering TPE to patients with pre-existing parenchymal lung injury.