Background and objectives: During partial liquid ventilation perfluorocarbons are instilled into the airways from where they subsequently evaporate via the bronchial system. This process is influenced by multiple factors, such as the vapour pressure of the perfluorocarbons, the instilled volume, intrapulmonary perfluorocarbon distribution, postural positioning and ventilatory settings. In our study we compared the effects of open and closed breathing systems, a heat-and-moisture-exchanger and a sodalime absorber on perfluorocarbon evaporation during partial liquid ventilation. Methods: Isolated rat lungs were suspended from a force transducer. After intratracheal perfluorocarbon instillation (10 mL kg−1) the lungs were either ventilated with an open breathing system (n = 6), a closed breathing system (n = 6), an open breathing system with an integrated heat-and-moisture-exchanger (n = 6), an open breathing system with an integrated sodalime absorber (n = 6), or a closed breathing system with an integrated heat-and-moisture-exchanger and a sodalime absorber (n = 6). Evaporative perfluorocarbon elimination was determined gravimetrically. Results: When compared to the elimination half-life in an open breathing system (1.2 ± 0.07 h), elimination half-life was longer with a closed system (6.4 ± 0.9 h, P < 0.01), a sodalime absorber (5.0 ± 0.6 h, P < 0.01) or a heat-and-moisture-exchanger (4.5 ± 0.8 h, P < 0.01). The combination of all three methods (7.1 ± 0.8 h) showed no significant additional effects (P > 0.05) when compared to a closed system. Conclusions: Evaporative perfluorocarbon loss can be reduced effectively with closed breathing systems, followed by the use of sodalime absorbers and heat-and-moisture-exchangers.