Computer modeling, particularly in the form of virtual patients, can be a useful tool for explaining complex phenomena associated with medical procedures. Based on interesting phenomena observed in 8 living patients undergoing large-volume therapeutic thoracentesis (TT) with pleural pressure (Ppl), transcutaneous oxygen and carbon dioxide pressures, and spirometric measurements, we formulated four questions regarding the impact of pleural effusion (PE) and TT on hemidiaphragm function and blood oxygenation. To answer these questions, we simulated right-sided PE in a virtual patient and studied changes in Ppl and lung volume during the respiratory cycle (exemplified by P-V loops, where P is Ppl in the ipsilateral hemithorax and V is the volume of both lungs), alveolar O2 (PAO2) and CO2 partial pressures and airflows in the main bronchi. The simulations suggest that: (a) the mediastinum compliance has a particular meaning for the work of both hemidiaphragms and explaining the 8-shape of P-V loops in hemidiaphragm inversion; (b) PAO2 is higher than normal before TT due to decreased ratio of the tidal volume to the volume of processed air at the end of expiration; and (c) in some patients, the Ppl amplitude related to breathing can be significantly greater before TT than later on.