Participants on spaceflights and international scientific analog Mars missions can encounter medical incidents (accidents, illnesses) and psychological issues (e.g., stress, group interaction, sleep disturbance, emotions). The aim of this study was to examine these parameters in a field crew living in a desert environment similar to Mars (Group 1) and in Mission Support Center (MSC) personnel on "Earth" (Group 2) during a 4-week mission. Of the 107 medical interventions in the field, 73 mainly minor incidents together with four near accidents and 29 medical checkup interventions were recorded. Of the 32 medical interventions, medical treatments for 23 incidents of minor severity were necessary in Group 2. Injuries (Group 1: 1.4/100 h, Group 2: 0.1/100 h) were significantly increased in the field, and illnesses (Group 1: 0.3/100 h, Group 2: 3.0/100 h) in the MSC personnel. Causes of accidents and illnesses are described. Psychological results show that emotions and stress remained stable in both groups. Sympathy, social competence, teamwork, and leadership showed high scores. These scores were lower on "Earth" but significantly increased in the last weeks. The Sahara's nighttime coldness was reflected in an increased wake-up frequency, and a longer sleeping time peaked in the third week, probably as a result of overfatigue. MARS2013 was a successful mission with highly motivated participants and minor medical incidents. For future analog missions and possibly long-distance open-space missions, some recommendations in terms of medical and psychological preparedness are made to reduce risks for field crew members and MSC personnel.