In response to exercise performed before or after altitude decompression, physiological changes are suspected to affect the formation and growth of decompression bubbles. We hypothesized that the work to change the size of a bubble is done by gas pressure gradients in a macro- and microsystem of thermodynamic forces and that the number of bubbles formed through time follows a Poisson process. We modeled the influence of tissue O₂ consumption on bubble dynamics in the O₂ transport system in series against resistances, from the alveolus to the microsystem containing the bubble and its surrounding tissue shell. Realistic simulations of experimental decompression procedures typical of actual extravehicular activities were obtained. Results suggest that exercise-induced elevation of O₂ consumption at altitude leads to bubble persistence in tissues. At the same time, exercise-enhanced perfusion leads to an overall suppression of bubble growth. The total volume of bubbles would be reduced unless increased tissue motion simultaneously raises the rate of bubble formation through cavitation processes, thus maintaining or increasing total bubble volume, despite the exercise.