Intertidal organisms, especially the sessile species, often experience long-term periodic air exposure during their lives. Learning the biochemical and physiological responses of intertidal organisms to long-term periodic air exposure and the relationship to duration of air exposure provides insight into adaptation to this variably stressful environment. We studied the Manila clam, Ruditapes philippinarum, an important species in world aquaculture, as a model to evaluate survival, growth, lipid composition, oxygen consumption, oxidative damage, and antioxidant enzyme activity in relation to the duration of air exposure in a long-term (60 days) laboratory study of varying durations of periodic emersion and re-immersion. Our results show: (1) clams undergoing a longer period of air exposure had lower survival and growth compared to those given a shorter exposure, (2) levels of oxidative damage and activities of antioxidant enzymes were higher in all air exposure treatments, but did not increase with duration of air exposure, and (3) the content of docosahexaenoic acid increased with duration of air exposure. Our results can largely be interpreted in the context of the energy expenditure by the clams caused by aerobic metabolism during the daily cycle of emersion and re-immersion and the roles of docosahexaenoic acid against oxidative stress.