Introduction: COVID-19 has trickle-down psychological effects on multiple strata of society, particularly university students. Apart from the worry of contracting or spreading COVID-19, Malaysian university students were also locked down on their campuses, suffering significant psychological distress. Hence, an online mindfulness intervention was proposed to alleviate psychological distress and improve psychological flexibility and mindfulness. Methods: This was a quasi-experimental study with university students as participants. Intervention group participants were instructed to complete online questionnaires which covered basic demographics and instruments assessing depression, anxiety, stress, mindfulness, psychological flexibility, and fear of COVID-19 before and after the one-hour intervention. The control group also completed before and after questionnaires and were subsequently crossed over to the intervention group. Repeated measures ANOVA was conducted to assess time*group effects. Results: 118 participants were involved in this study. There were significant differences in anxiety (F (1,116) = 34.361, p < 0.001, partial eta-squared = 0.229) and psychological flexibility between the two groups (F (1,116) = 11.010, p = 0.001, partial eta-squared = 0.087), while there were no differences in depression, stress, mindfulness, or fear of COVID-19. Conclusion:The results of this study corroborate the efficacy of online single-session mindfulness therapy as a viable short-term psychological intervention under financial and time constraints. Since university students are in the age group with the highest incidence of depressive and anxiety disorders, it is crucial to utilize resources to address as many students as possible to ensure maximum benefit.