Background: The COVID-19 related lockdown and home confinement might have an important impact on the quality of life in enterprise workers. We investigated the quality of life during the epidemic in enterprise workers who just returned to work, and assessed its potential influencing factors to have a better understanding of the impact of COVID-19 epidemic lockdown and home confinement. Methods: This was a cross-sectional study of enterprise workers conducted in Deqing and Taizhou, Zhejiang Province, China. The Chinese version of EQ5D was used to assess life quality, and information about general characteristics and COVID-19 related factors was collected by a structured questionnaire, which was distributed through the social application “WeChat”. Results: A total of 2,435 participants were enrolled, 59.5% of which worked in Deqing. About 50% of the participants reported worries about the COVID-2019 epidemic and 40.1% had a centralized or home quarantine during the epidemic. The mean EQ-5D score and VAS were 0.990 and 93.5. Multiple logistic regression showed that the quality of life measures was related to physical activities (ORad=0.46) and keeping home ventilation (ORad=0.04) in Deqing, and were related to wearing a mask when going out (ORad=0.35), keeping home ventilation (ORad=0.16), unmarried status (ORad=2.38) and having a centralized or home quarantine (ORad=1.64) in Taizhou,Conclusions: The quality of life for returning enterprise workers in areas with different risks of COVID-19 was affected by different factors. Associated factors identified from this study would help develop proper intervention measures for enterprise workers to reduce the impact of large-scale public health events like the COVID-19 on their quality of life.