Background and Objectives: Fibromyalgia (FM) is a chronic and complex condition characterized by widespread pain, fatigue, psychological burden, and cognitive impairment, posing significant challenges for treatment. Immersive virtual reality exercise (iVRE) has been proposed as an innovative therapeutic approach to increase adherence, motivation, and multidimensional benefits, but evidence in FM remains limited. This study aimed to evaluate the effects of a six-week iVRE program on cortisol levels, quality of life, cognitive function, and psychological symptoms in women with FM. Materials and Methods: A quasi-experimental pre–post design was conducted with 21 women (mean age 48.1 ± 10.7 years) diagnosed with FM, who completed twelve 30 min sessions of iVRE using Oculus Quest 2™ and the FitXR platform. Outcomes assessed pre- and post-intervention included salivary cortisol (ELISA), quality of life (FIQR), emotional status (DASS-21), and cognitive function (MoCA). Adherence and safety were monitored throughout. Results: The intervention was well tolerated, with no adverse events and 100% adherence. Statistically significant improvements were observed in FIQR scores (p < 0.001, d = 3.54), depression (p < 0.001, d = 1.19), anxiety (p < 0.001, d = 1.39), and stress (p < 0.001, d = 2.28). Cognitive performance improved significantly, with higher MoCA total scores (p < 0.001, d = 1.52) and better outcomes in visuospatial ability, language, and delayed recall domains. No significant changes were detected in salivary cortisol levels (p = 1.000). Conclusions: A six-week iVRE program is safe and feasible, promoting clinically relevant improvements in quality of life, emotional well-being, and cognitive function in women with FM, despite the absence of changes in cortisol. These findings highlight iVRE as a promising complementary therapeutic strategy within multidisciplinary FM management, warranting further controlled studies with larger samples and long-term follow-up to confirm its efficacy and explore underlying mechanisms.

Fibromyalgia (FM) is associated with altered pain modulation and heterogeneous responses to exercise. Exercise-induced hypoalgesia (EIH), typically observed in healthy individuals, appears inconsistent in FM. Immersive virtual reality-based exercise (VRBE) may influence pain through cognitive and attentional mechanisms, but its relationship with EIH remains unclear. This study aimed to identify exploratory response patterns based on changes in pressure pain thresholds (ΔPPT) following a single VRBE session and to explore associations with clinical and cognitive variables. A secondary pre–post analysis was conducted in 35 women with FM who completed a standardized VRBE protocol. PPTs were assessed at the trapezius, lumbar region, and knee before and after the intervention. K-means clustering was applied to ΔPPT values, and repeated measures ANOVA evaluated time × cluster interactions. No significant group-level changes in PPT were observed (p ≥ 0.432). Three response patterns were identified: positive responders (17%), negative responders (23%), and non-responders (60%), with significant time × cluster interactions across all sites (p < 0.001). Cognitive function and educational level were associated with ΔPPT but did not predict cluster membership. These findings indicate interindividual variability in EIH responses following VRBE in FM, highlighting the potential relevance of individualized monitoring during VR-based exercise interventions and the need for further investigation of underlying mechanisms.

Fibromyalgia is a chronic pain condition associated with reduced quality of life, psychological symptoms, cognitive impairment, and low adherence to exercise-based interventions. Immersive virtual reality (IVR) has gained attention as a rehabilitation approach; however, the relationship between user experience, adherence, and clinical outcomes remains unclear. This post hoc exploratory secondary analysis was derived from a randomized controlled clinical trial (NCT07605143) and included 16 women with fibromyalgia who completed a six-week IVR-based rehabilitation program. Associations between user experience, adherence, and clinical outcomes were explored among participants exposed to IVR. Quality of life was assessed using the Fibromyalgia Impact Questionnaire-Revised (FIQ-R), psychological symptoms using the Depression Anxiety Stress Scales (DASS-21), and user experience using the Player Experience of Need Satisfaction (PENS) questionnaire. Within-group changes were observed in FIQ-R scores (p = 0.001; d = 1.08) and DASS-21 stress levels (p = 0.025). Participants demonstrated favorable adherence and positive user experience. A significant correlation was identified between intuitive control and changes in depression scores (ρ = 0.63, p = 0.008). This exploratory analysis identified favorable user experience and adherence among women participating in an IVR-based rehabilitation program. However, due to the absence of a concurrent control group, no conclusions regarding treatment efficacy can be drawn. These findings should be considered hypothesis-generating.