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This study aimed to investigate the effect of a VR-based stress management program on people with mood disorders. A quasi-experimental study was conducted in a tertiary hospital in Singapore, and a convenience sample of 22 was recruited. The program comprised three daily 1-hour sessions incorporating psychoeducation and VR-based relaxation practice. Participants who completed the program had significantly lowered subjective stress (t = 6.91, p < 0.001), depression (t = 5.62, p < 0.001), and anxiety (t = 5.54, p < 0.001); and increased skin temperature (F = 17.71, p < 0.001), perceived relaxation (F = 26.20, p < 0.001) and knowledge (F = 13.77, p < 0.001). Participants' feedback on the program was positive. Findings from this study contribute to improving clinical practice and serve as preliminary data to conduct more rigorous research in the future.