Background: The COVID-19 pandemic is generating extreme psychological stress associated with sadness, grief, irritability, and mood swings. Virtual reality (VR) is an immersive technology that may enhance individuals’ personal efficacy, emotional response, and wellbeing.Objective: We aimed to conduct a single-cohort, controlled trial with a 2:1 (waiting-list – VR protocol) allocation for a self-administered at-home weekly VR-based protocol for reducing the psychological burden experienced during the COVID-19 lockdown in Italy.Methods: A national convenience sample of individuals having experienced at least two months of strict social distancing measures (including the stay-at-home order) experienced the following weekly protocol (“COVID Feel Good”, available online here: www.covidfeelgood.com) consisting of two integrated parts: the first part consists of a 10-minute 360° VR video entitled “Secret Garden” and the second part includes a series of social exercises, with a specific goal for each day of the week. Half of the sample experienced the VR video on the smartphone only, while the other half experienced the VR video using an immersive headset. Primary outcome measures were depressive, anxiety and stress symptoms (measured using the DASS-21, the PSS and the BHS scales). Secondary outcomes were the experienced social connectedness and the level of fear experienced during the COVID-19 pandemic (measured using the SCS and FCOR scales). Analytic methods included different separate linear mixed-effects models.Results: The study sample was 40 adults [18 females; mean age 30.3± 12.00 (range: 21–65)]. Results indicated no significant changes (P=1.000) in study variables between the waiting period (i.e., data collected 7 days before the start of the treatment) and the baseline (i.e., data collected at the beginning of the intervention, T0). Participants exhibited improvement from baseline to postintervention for almost all primary variables (all Ps < 0.05), except for the perceived hopelessness (P=0.1098). Results for the secondary outcomes indicated an increase in social connectedness from T0 to T1 (P=0.0327), but not a significant reduction in the perceived fear of Coronavirus (P=0.4121). Results indicated that treatment positive effects were stable at the 2-weels of follow-up for all study variables, except for depressive symptoms. None of the models were significant on the factor “Immersion”, suggesting that there is no significant effect of the modality (immersive vs non immersive) on the results of the treatment.Conclusions: This pragmatic pilot trial tried to understand if and how a weekly VR self-help protocol can help individuals in overcoming the psychological burden associated with spread of the COVID-19 and the consequent health emergency. The results, even if preliminary, suggest the efficacy of the proposed protocol. Moreover, its current availability in 12 different languages - English, Spanish, French, Brazilian/Portuguese, German, Italian, Turkish Japanese, Korean, Farsi, Romanian and Catalan – make COVID Feel Good a free and effective choice for helping individuals worldwide to cope with the psychological distress related to the COVID-19 crisis.