We report on the detection of microorganisms onboard the International Space Station (ISS) using an electronic nose we named the E-Nose. The E-Nose, containing an array of ten different metal oxide gas sensors, was trained on Earth to detect the four most abundant microorganisms that are known to exist onboard the ISS. To assess its performance in space, the E-Nose was brought to the ISS and three measurement campaigns were carried out in three different locations inside the ISS during a 5-month mission. At the end of this mission, all investigated locations were wiped with swabs, and the swabs and odor sensor signal data were sent back to Earth for an in-depth analysis in earthbound laboratories. The in-space measurements were compared with an odor database containing four organisms, but a consensus odor could not be identified. Microbiological results could not provide clues to the smell that was measured. The yeast Rhodotorula mucilaginosa was identified in the literature as the most probable candidate for the unknown odor. Further investigations showed that the smell of Rhodotorula mucilaginosa matches very well with the data obtained inside the ISS. Finally, Rhodotorula mucilaginosa DNA was identified in swabs taken from the sleeping cabin of the astronaut, which confirms the assumption that the yeast Rhodotorula mucilaginosa was actually measured in space by the E-Nose.