Background After a prolonged intensive care unit (ICU) stay, approximately 50%-75% of all critically ill patients suffer from neurocognitive late effects and a reduction of health-related quality of life. It is assumed that the noisy and stressful ICU environment leads to sensory overload and deprivation and potentially to long-term cognitive impairment. Objective In this study, we investigated three different virtual reality environments and their potentially restorative and relaxing effects for reducing sensory overload and deprivation in the ICU. Methods A total of 45 healthy subjects were exposed to three different environments, each 10 minutes in length (dynamic, virtual, natural, and urban environments presented inside the head-mounted display, and a neutral video on an ICU TV screen). During the study, data was collected by validated questionnaires (ie, restoration and sickness) and sensors to record physiological parameters (240 hertz). Results The results showed that the natural environment had the highest positive and restorative effect on the physiological and psychological state of healthy subjects, followed by the urban environment and the ICU TV screen. Conclusions Overall, virtual reality stimulation with head-mounted display using a dynamic, virtual and natural environment has the potential, if directly used in the ICU, to reduce sensory overload and deprivation in critically ill patients and thus to prevent neurocognitive late effects.