The COVID-19 pandemic imposed extreme living conditions of social distancing, which triggered negative mental health problems and created challenges in seeking mental health support. Mindfulness-based interventions (MBIs) have been found to enhance wellbeing and mental health by reducing stress and anxiety and improving emotion regulation. Preliminary evidence suggests that online, synchronous MBIs may produce beneficial effects similar to face-to-face programs. However, the effectiveness of such online-MBIs to support mental health in highly stressful times, such as a global pandemic, requires further study. To this end, we investigated the effect of an online 8-week Mindfulness-Based Stress Reduction (MBSR) program on aspects of mental health during the first wave of the COVID-19 pandemic. Participants (N=92) who expressed interest in discounted online-MBSR programs were recruited for the study. The division into experimental and control groups was based on actual enrollment to the courses. Those who enrolled in a program were assigned to the experimental condition and those who decided not to enroll served as controls. Participants were assessed pre-intervention, post-intervention, and 1-month post-intervention for levels of mindfulness, perceived stress, anxiety, emotion regulation, and intolerance of uncertainty. Differences between the groups were tested using the general linear mixed effects model (GLMM) and Individual Growth Curve Models (IGCM) in intent to treat analysis. The findings indicated that, relative to the control group, MBSR improved mindfulness abilities (p <0.001), decreased anxiety (p <0.001), and stress (p <0.001) and increased emotion regulation (p <0.001). These effects were found to persist 1 month after the end of the program, despite the increased governmental public-health restrictions due to COVID-19 at that time. The ability to tolerate uncertainty, a central characteristic of the pandemic, was not found to be affected by the program. A mediation analysis revealed that the effect of the intervention on mental health improvement was partially mediated by the improvement in emotion regulation. Overall, the findings provide positive evidence for the feasibility of an online-MBSR program to support the mental health of individuals from the general population through the mediation of emotion regulation in challenging times, such as a global pandemic.