After prolonged stay in an intensive care unit (ICU) patients often complain about cognitive impairments that affect health-related quality of life after discharge. The aim of this proof-of-concept study was to test the feasibility and effects of controlled visual and acoustic stimulation in a virtual reality (VR) setup in the ICU. The VR setup consisted of a head-mounted display in combination with an eye tracker and sensors to assess vital signs. The stimulation consisted of videos featuring natural scenes and was tested in 37 healthy participants in the ICU. The VR stimulation led to a reduction of heart rate (p = 0. 049) and blood pressure (p = 0.044). Fixation/saccade ratio (p < 0.001) was increased when a visual target was presented superimposed on the videos (reduced search activity), reflecting enhanced visual processing. Overall, the VR stimulation had a relaxing effect as shown in vital markers of physical stress and participants explored less when attending the target. Our study indicates that VR stimulation in ICU settings is feasible and beneficial for critically ill patients.