The COVID-19 pandemic poses a threat to global public health due to home confinement policies impacting on physical activity engagement and overall health. This study aimed to explore physical activity participation, health-related quality of life (HRQoL), and levels of perceived stress among Chinese adults during the COVID-19 pandemic. An online survey was conducted between 25 February and 15 March 2020. A total of 645 surveys were completed. Participants reported increased sedentary time from pre-COVID-19 period to the COVID-19 pandemic period (p < 0.05). Over 80% of the sample engaged in either low or moderate intensity physical activity. Participants’ average physical component summary score (PCS) and mental component summary score (MCS) for HRQoL were 75.3 (SD = 16.6) and 66.6 (SD = 19.3), respectively. More than half of participants (53.0%) reported moderate levels of stress. Significant correlations between physical activity participation, HRQoL, and levels of perceived stress were observed (p < 0.05). Prolonged sitting time was also found to have a negative effect on HRQoL (p < 0.05). During such periods of home confinement, public health strategies aimed at educating Chinese adults to enhance home-based physical activity may be necessary to maintain health on a population level.