Objectives The objective of this study was to examine the effectiveness of mindfulness-based stress reduction (MBSR) on depression, anxiety and psychological distress across populations with different chronic somatic diseases. Methods A systematic review and meta-analysis were performed to examine the effects of MBSR on depression, anxiety, and psychological distress. The influence of quality of studies on the effects of MBSR was analyzed. Results Eight published, randomized controlled outcome studies were included. An overall effect size on depression of 0.26 was found, indicating a small effect of MBSR on depression. The effect size for anxiety was 0.47. However, quality of the studies was found to moderate this effect size. When the studies of lower quality were excluded, an effect size of 0.24 on anxiety was found. A small effect size (0.32) was also found for psychological distress. Conclusions It can be concluded that MBSR has small effects on depression, anxiety and psychological distress in people with chronic somatic diseases. Integrating MBSR in behavioral therapy may enhance the efficacy of mindfulness based interventions.