Background: Women with Vulvodynia experience pain, related impacts on sex and daily functioning, and depression. While psychosocial factors are associated with outcomes in Vulvodynia, longitudinal data are limited, especially in mixed/spontaneous Vulvodynia. Broad psychological models such as psychological flexibility (PF) and content-specific factors, such as body-exposure anxiety (BEA) and avoidance during sexual activities and perceived injustice, have not been adequately investigated in Vulvodynia. The aim of this study was to explore whether these factors assessed at baseline predict pain severity, pain interference, sexual functioning and satisfaction and depression 3 months later. Methods: A longitudinal study of 349 women with Vulvodynia was conducted. Participants completed online self-report measures of pain-related and sexual outcomes, depression, BEA, perceived injustice and facets of PF (present moment awareness, pain acceptance, committed action) at baseline and after 3 months, overlapping with the Coronavirus disease 2019 (COVID-19) pandemic. Results: Seventy percent of women responded at both assessments (n = 244). There were significant decreases in pain severity, pain interference, present moment awareness, committed action and a significant increase in depression at 3 months. All the baseline psychosocial factors significantly correlated with at least one outcome at 3 months. When adjusting for baseline outcome and demographics, committed action significantly positively predicted depression at 3 months and pain acceptance significantly positively predicted pain interference at 3 months. Conclusions: Among women with Vulvodynia, pain acceptance and committed action are prospectively associated with pain interference and depression. The reliability and generalizability of these results needs to be established given the overlap with the COVID-19 pandemic. Future studies should investigate whether targeting these factors enhances outcomes in Vulvodynia. Significance: This longitudinal study explored the role of PF, perceived injustice and body image during sexual activities in predicting pain severity, pain interference, sexual functioning, sexual satisfaction and depression in women with Vulvodynia. The study findings reveal that two facets of PF (committed action and pain acceptance) predicted pain interference and depression over time. It may be important to incorporate these processes in treatments developed for Vulvodynia.