Accumulation and breakdown of large algal blooms often causes serious hypoxia in lakes, representing a major potential threat to zooplankton grazers such as Daphnia. Generally, populations comprise different age groups, whose molecular responses to environmental stressors are different. The aim of our study was to investigate the age-dependent effects of oxygen depletion on D. magna survival and selected gene expressions of energy-relevance and stress-defense. Four age groups of D. magna (1, 4, 7 and 14 days) were exposed to 0.0625, 0.125, 0.25 mM dissolved oxygen (DO) for 48 h. Results showed that survival rates of 14-day-old individuals in 0.0625 mM DO and 0.125 mM DO were much lower than those in 0.25 mM DO, while no significant difference was found in remaining age groups. Low DO up-regulated hemoglobin expression compared with the controls in all age groups; the similar pattern in α-esterase was observed when 1-day-old individuals were exposed to 0.0625 mM, 4- and 7-day-old individuals at 0.125 mM, respectively. HSP70 and CAT expression were significantly upregulated in 1- and 7-day-old individuals exposed to 0.125 mM. The findings indicate that age structure should be taken into account when interpreting dynamics of Daphnia populations affected by oxygen depletion. Age may modify energy reallocation and alter susceptibility of the organisms.