Labyrinth seals, extensively used in space applications, serve to prevent the loss of liquid lubricants and shield satellite subsystems from contamination. These seals are essential for the reliable functioning of bearings and for protecting satellite subsystems from contamination. This study compares analytical predictions of lubricant loss against experimental measurements and computer simulations to optimize labyrinth seal configurations. Analytical models tend to overestimate mass loss by 5–8 times compared to experimental data, indicating limited reliability for complex seal geometries. Simulations using MolFlow+ and COMSOL Multiphysics align closely with experimental results, providing accurate mass loss predictions. Key findings highlight that labyrinth length, width, and surface roughness are critical factors in minimizing evaporative mass loss. Notably, stepped labyrinth seals with relief grooves and optimized step positioning effectively reduce molecular beaming effects and improve sealing performance compared to straight geometries. Effective sealing not only reduces mission failures but also helps to minimize space debris, thereby promoting safer satellite missions.