Healthcare workers have experienced increased occupational health risks caused by COVID-19 disease. The purpose of this project was to examine the relationships between reporting COVID-19 symptoms by employees in a healthcare institution in the United States and employees’ demographics, vaccination status, co-morbid conditions, and body mass index (BMI). This project employed a cross-sectional design. It involved the analysis of data on COVID-19 exposure and infection incidents among employees in the healthcare institution. The dataset contained more than 20,000 entries. The results indicate that being female, African American, between 20 and 30 years old, diagnosed with diabetes, diagnosed with chronic obstructive pulmonary disease (COPD), or on immunosuppressive medicines is associated with greater reporting of COVID-19 symptoms by the employees. Furthermore, BMI is associated with reporting COVID-19 symptoms; the higher the BMI, the greater the likelihood of reporting a symptomatic infection. Moreover, having COPD, being 20–30 years old, being 40–50 years old, BMI, and vaccination status were significantly associated with employees reporting symptoms while controlling for other variables associated with reporting the symptoms among the employees. These findings may be applicable to other infectious disease outbreaks or pandemics.