There are limited reports on the relationship between spirituality and mental stress in PLWH in China, who may be subject to anti-religious pressures from the government. In this study, we aimed to understand whether spirituality influences Chinese PLWH's mental stress and, if so, at what level. We recruited 200 PLWHs from Beijing's Ditan Hospital to complete a cross-sectional survey inquiring about their practice of spirituality as well as their level of mental stress. The study found that PLWH who presented with a mid-level of spirituality have the highest mental stress when compared to those who have a low level of spiritual beliefs or a high level of spiritual beliefs. This study points to the utility of healthcare providers taking PLWH's potential spirituality into consideration, perhaps in particular for those with a moderate level of spirituality, in order to provide the most comprehensive care possible.