Objective <p>Child and adolescent depression is an increasing concern, significantly impacting their emotional, academic, and social well-being. While mindfulness-based interventions have shown effectiveness in reducing depressive symptoms, emerging technologies like virtual reality offer more engaging approaches. This study aimed to investigate the moderating effects of a virtual mindfulness programme ("Virtual EMO-Mind") in children, focusing on how neuroticism, pre-existing mindfulness skills, and demographic factors influence changes in depressive symptoms and mindfulness skills.</p> Method <p>Participants were 432 students aged between 9 and 12&#xa0;years (<i>M</i>_age = 10.63; <i>SD</i>_age = 0.71; 53.6% girls and 46.4% boys). Paired-sample <i>t</i>-tests were conducted to assess changes in depression and mindfulness before and after the intervention. Additionally, ANCOVA and linear regression were employed to analyse the moderating effects of neuroticism, baseline mindfulness, and demographic factors on these changes.</p> Results <p>The results showed that neuroticism significantly moderated negative dimensions of depression, but this effect was no longer significant after controlling for initial symptom levels. Higher neuroticism was associated with less improvement in Pleasure and reduced gains in mindfulness skills. Baseline mindfulness levels did not predict changes in depression, although participants with lower initial mindfulness skills experienced greater improvements. Gender and age did not moderate outcomes.</p> Conclusions <p>This study found no significant moderating effect of neuroticism on depressive symptoms in children, contrary to findings in adult populations. Future studies should consider longer interventions, tailored assessments for children, and a broader age range to gain a more comprehensive understanding of the moderating effects of neuroticism and other factors in mindfulness-based interventions.</p> Preregistration <p>This study is not preregistered.</p>