Background: It is well established that even moderate levels of alcohol affect cognitive functions such as memory, self-related information processing, and response inhibition. Nevertheless, the neural mechanisms underlying these alcohol-induced changes are still unclear, especially on the network level. The default mode network (DMN) plays an important role in memory and self-initiated mental activities; hence, studying functional interactions of the DMN may provide new insights into the neural mechanisms underlying alcohol-related changes. Methods: We investigated resting-state functional connectivity (rsFC) of the DMN in a cohort of 37 heavy drinkers at a breath alcohol concentration of 0.8 g/kg. Alcohol and saline were infused in a single-blind crossover design. Results: Intranetwork connectivity analyses revealed that participants showed significantly decreased rsFC of the right hippocampus and right middle temporal gyrus during acute alcohol exposure. Moreover, follow-up analyses revealed that these rsFC decreases were more pronounced in participants who reported stronger craving for alcohol. Exploratory internetwork connectivity analyses of the DMN with other resting-state networks showed no significant alcohol-induced changes, but suffered from low statistical power. Conclusions: Our results indicate that acute alcohol exposure affects rsFC within the DMN. Functionally, this finding may be associated with impairments in memory encoding and self-referential processes commonly observed during alcohol intoxication. Future resting-state functional magnetic resonance imaging studies might therefore also investigate memory function and test whether DMN-related connectivity changes are associated with alcohol-induced impairments or craving.