Nature exposure in virtual reality (VR) can provide emotional well-being benefits for people who cannot access the outdoors. Little is known about how these simulated experiences compare with real outdoor experiences. We conduct an experiment with healthy undergraduate students that tests the effects of 6 min of outdoor nature exposure with 6 min of exposure to a 360-degree VR nature video, which is recorded at the outdoor nature exposure location. Skin conductivity, restorativeness, and mood before and after exposure are measured. We find that both types of nature exposure increase physiological arousal, benefit positive mood levels, and are restorative compared to an indoor setting without nature; however, for outdoor exposure, positive mood levels increase and for virtual nature, they stay the same. The nature-based experience shows benefits above and beyond the variance explained by participants’ preferences, nature and VR experiences, and demographic characteristics. Settings where people have limited access to nature might consider using VR nature experiences to promote mental health.