OBJECTIVES: This study investigated (1) the effect of engaging with 20-minute simulated natural environments delivered via virtual reality (VR) on current mood state and (2) the effect of engaging with multiple VR sessions over a period of a week on the depressive symptoms of people with a spinal cord injury (SCI). DESIGN: Randomized controlled trial design. SETTING: Spinal Cord Injury Rehabilitation Unit in Australia. PARTICIPANTS: Participants (N=24) were assigned to a group engaging in VR sessions during week 1 (group 1, n=10) or week 2 (group 2, n=14). INTERVENTIONS: The intervention week involved participation in up to three 20-minute VR sessions over 3 consecutive days. The control condition involved regular rehabilitation practice over a week. MAIN OUTCOME MEASURES: The Patient Health Questionnaire-8 (PHQ-8) was completed prior to the first week (T1), after the first week and prior to the second week (T2), and after the second week (T3). Current feeling states, including depressed/happy, anxious/relaxed, and not feeling good/feeling good, were rated immediately prior and after each VR session. RESULTS: Levels of happiness, relaxation, and feeling good were significantly higher subsequent to engaging with each VR session. Between-group differences in PHQ-8 scores were significantly greater for participants who experienced the intervention during the first week compared to participants within the control group: intervention participants had significant improvements in psycho-emotional health. Within-group PHQ-8 scores were reduced for each group subsequent to experiencing the intervention; however, differences were not significant. CONCLUSIONS: Engaging with simulated natural environments delivered via VR can favorably affect the psycho-emotional health of people with SCI receiving rehabilitation in hospital. Future research including larger samples and investigating the effect over a longer time period is required to confirm the findings presented.