Disorders of Consciousness (DoCs) after severe acquired brain injury involve substantial impairment of cognition and physical functioning, requiring comprehensive rehabilitation and support. Technological interventions, such as immersive Virtual Reality (VR), have shown promising results in promoting neural activity and enhancing cognitive and motor recovery. VR can induce physical sensations that may activate the Autonomic Nervous System (ANS) and induce ANS-regulated responses. This study aimed to investigate the effects of immersive VR on the ANS in patients with DoCs through the analysis of the electrodermal activity (EDA). EDA was measured with a wearable device during a single immersive VR session consisting of static and dynamic videos depicting naturalistic environments. A pilot case–control study was conducted with 12 healthy participants and 12 individuals with DoCs. Results showed higher EDA values in patients than in healthy participants (p = 0.035), suggesting stronger autonomic activation during immersive VR exposure, while healthy subjects, in turn, showed a decrease in EDA values. Our results revealed a significant interaction between conditions and groups (p = 0.003), with patients showing significantly increased EDA values from the baseline compared to dynamic video observation (p = 0.014) and final rest (p = 0.007). These results suggest that immersive VR can elicit sympathetic arousal in patients with DoCs. This study highlights the potential of immersive VR as a tool to strengthen autonomic responses in patients with impaired consciousness.