(1) Background: Post-COVID syndrome is defined as symptoms that occur simultaneously with or after a COVID-19 infection, last for 12 weeks, and are not due to another diagnosis. Limited data are available on people’s long-term quality of life following a COVID-19 infection. The aim of this cross-sectional study was to investigate the long-term quality of life after COVID-19 among employees of a hospital in Germany and to identify risk factors. (2) Methods: A monocentric, cross-sectional study was conducted using the validated and digitized WHOQOL-BREF questionnaire via Netigate® between 10/2022 and 02/2023. Data on the quality of life and global health status were collected in the following four domains: physical health, mental health, social relationships, and the environment. (3) Results: The response rate was 73.8 % (923/1250). Furthermore, 63.4 % of the hospital staff respondents reported at least one persistent symptom after a COVID-19 infection, leading to significant differences in quality of life. Pre-existing conditions, persistent symptoms, and disabilities after a COVID-19 infection as well as a high BMI, no partnership, and a low educational level were found to significantly contribute to a low long-term quality of life. (4) Conclusions: Obesity, a lack of partnership, and a low level of education were independent risk factors for a lower quality of life post-COVID-19 infection in this cohort of hospital staff. Further multicenter studies are required to validate the incidence and their suitability as independent risk factors for post-COVID syndrome.