Although many studies have investigated burnout, stress, and mental health issues among health care workers (HCWs) during the COVID-19 pandemic, few have linked these relationships to chronic physiological illnesses such as cardiovascular diseases. This study assessed changes in cardiovascular risk factors in HCWs and other hospital workers during the COVID-19 pandemic and identified vulnerable groups at a higher risk of increased adverse cardiovascular conditions. Five hundred and fourteen hospital employees ≥ 20 years of age underwent physical examinations and laboratory testing once before and once after the first wave of the pandemic in Taiwan during 2020 and 2021. Their sociodemographic characteristics and cardiovascular risk factors, including blood pressure, blood biochemical parameters, and body mass index, were collected. The differences between pre- and post-pandemic measurements of their biophysical and blood biochemical parameters were analyzed using pairwise tests. The post-pandemic increases in their parameter levels and cardiovascular risk as a function of underlying factors were estimated from multivariate regressions. HCWs showed significant increases in levels and abnormal rates of BMI, blood pressure, plasma glucose, and total cholesterol after the pandemic. Post-pandemic increases in BMI, waist circumference, and blood pressure were higher in females than in males. Workers with higher levels of education or longer job tenure had greater increases in BMI, triglyceride, and total cholesterol levels than other workers. Females had a higher incidence of abnormal BMI and hypertension than males (adjusted odds ratios [AORs] of 8.3 and 2.9, respectively). Older workers’ incidence of hypertension was higher than younger workers’ (AOR = 3.5). Preventive strategies should be implemented for HCWs susceptible to cardiovascular diseases during emerging infectious disease outbreaks.