The neurobehavioral risks associated with spaceflight are not well understood. In particular, little attention has been paid on the role of resilience, social processes and emotion regulation during long-duration spaceflight. Bed rest is a well-established spaceflight analogue that combines the adaptations associated with physical inactivity and semi-isolation and confinement. We here investigated the effects of 30 days of 6 degrees head-down tilt bed rest on affective picture processing using event-related potentials (ERP) in healthy men. Compared to a control group, bed rest participants showed significantly decreased P300 and LPP amplitudes to pleasant and unpleasant stimuli, especially in centroparietal regions, after 30 days of bed rest. Source localization revealed a bilateral lower activity in the posterior cingulate gyrus, insula and precuneus in the bed rest group in both ERP time frames for emotional, but not neutral stimuli.