<p>The crucial necessity to cope with oxidative stress caused not only by external factors but also by the cellular intermediary metabolism has driven the selection of diverse protection mechanisms in strict anaerobic microorganisms. In this context <i>Methanosarcina acetivorans</i>, a marine archaeon, expresses diverse functional enzymes involved in the protection against oxidative stress induced by O₂. However, enzymes involved in aldehyde metabolism/detoxification that may have an important role as part of the antioxidant machinery have not yet been evaluated. In this work, the transcriptomic regulation of 8 genes encoding putative aldehyde dehydrogenases (ALDH) and the enzymatic activity were evaluated in <i>M. acetivorans</i> cells grown in the presence of air as an external stressor, and compared with cells grown under anaerobic conditions. The presence of air induced significant higher content of aldehydes, however the air exposition prepared the cells for oxidative stress as judged by changes in the ROS production rate with respect to anaerobic-grown control cells. Transcript levels of 5 ALDH codifying sequences tested were up-regulated, while 3 sequences were down-regulated by the presence of air. Basal ALDH activity levels were detected in anaerobic-grown cells with NAD⁺ or methylviologen as electron acceptor, suggesting a role of these enzymes in the central metabolism under anaerobic conditions. However, ALDH activity was significantly incremented in cells grown in the presence of air. Incubation of cells with acetaldehyde was toxic for anaerobic cells, but it was tolerated and detoxified in cultures grown with air. Results suggested that in <i>M. acetivorans</i>, ALDHs play a key role metabolizing aldehydes produced as part of the central metabolism, but also in combating oxidative stress induced by air exposure episodes.</p>