BACKGROUND: Attempts to use virtual reality (VR) as a treatment for various psychiatric disorders have been made recently, and many researchers have identified the effects of VR in psychiatric disorders. Studies have reported that VR therapy is effective in social anxiety disorder (SAD). However, there is no prior study on the neural correlates of VR therapy in patients with SAD. OBJECTIVE: The aim of this study is to find the neural correlates of VR therapy by evaluating the treatment effectiveness of VR in patients with SAD using portable functional near-infrared spectroscopy (fNIRS). METHODS: Patients with SAD (n=28) were provided with 6 sessions of VR treatment that was developed for exposure to social situations with a recording system of each participant's self-introduction in VR. After each VR treatment session, the first-person view (video 1) and third-person view (video 2) clips of the participant's self-introduction were automatically generated. The functional activities of prefrontal regions were measured by fNIRS while watching videos 1 and 2 with a cognitive task, before and after whole VR treatment sessions, and after the first session of VR treatment. We compared the data of fNIRS between patients with SAD and healthy controls (HCs; n=27). RESULTS: We found that reduction in activities of the right frontopolar prefrontal cortex (FPPFC) in HCs was greater than in the SAD group at baseline (t=-2.01, P=.049). Comparing the frontal cortex activation before and after VR treatment sessions in the SAD group showed significant differences in activities of the FPPFC (right: t=-2.93, P<.001; left: t=-2.25, P=.03) and the orbitofrontal cortex (OFC) (right: t=-2.10, P=.045; left: t=-2.21, P=.04) while watching video 2. CONCLUSIONS: Activities of the FPPFC and OFC were associated with symptom reduction after VR treatment for SAD. Our study findings might provide a clue to understanding the mechanisms underlying VR treatment for SAD. TRIAL REGISTRATION: Clinical Research Information Service (CRIS) KCT0003854; https://tinyurl.com/559jp2kp.