The aim of present study was to determine the effects of a 60-day head-down tilt long-term bed rest (HDT) on stress and recovery in sixteen healthy young female volunteers. Participants were randomly assigned to either an exercise group (Exe) that followed a training program combining resistive and aerobic exercises, or to a no-exercise control group (Ctl). Psychological states were assessed using the Rest-Q, a validated questionnaire based on stress– recovery responses. A longitudinal analysis revealed significant changes in the general and specific-stress scales for all participants throughout the experiment with a critical stage from supine to standing posture leading to a significant decrease in physical recovery. During HDT, Exe reported higher scores on stress subscales, as well as lower recovery scores compared to the Ctl. During the post-HDT ambulatory recovery period, the exercisers still reported higher scores than the non-exercisers on the Lack of energy stress-related scale, along with lower scores in general wellbeing and personal accomplishment. The present findings show that simulated weightlessness such as HDT may induce psychological stress and lead to subsequent alterations in perceived recovery. Exercise did not reduce HDT impaired effects on stress and recovery states. Several suggestions, including psychological preparation, are proposed to support the beneficial effects of exercise on psychological factors.