Abstract Background Healthcare workers (HCWs) is the high-risk group for COVID-19 infection due to increased workplace exposure. However, evidence of the disease burden and factors associated with severe COVID-19 infection among HCWs is limited. Therefore, this article aims to describe the prevalence of severe COVID-19 disease among HCWs in Sabah, Malaysia, and to determine the factors associated with severe COVID-19 infection. Method A retrospective cross-sectional study was carried out by assessing the data of COVID-19-infected HCWs in Sabah, Malaysia, from 1st March 2021 until 30th September 2021. Logistic regression analysis was used in this study. Results Three thousand and forty HCWs were diagnosed with COVID-19 from 1st March 2021 until 30th September 2021. Of the 3040 HCWs, 2948 (97.0%) HCWs were mild, whereas 92 (3.0%) were severe. The multivariate logistic regression model showed that severe COVID-19 among HCWs in Sabah was associated with those do not receive any COVID-19 vaccination (aOR 6.061, 95% CI 3.408 – 10.780), underlying co-morbidity (aOR 3.335, 95% CI 2.183 – 5.096), and female (aOR 1.833, 95% CI 1.090 – 3.081). Conclusion HCWs should strictly adhere to preventive measures, including vaccination, personal protective equipment, and early referral to a physician upon identifying severe COVID-19 infection. Early screening and aggressive co-morbidity treatment among HCWs are essential for public health practitioners to prevent severe COVID-19 disease. Regardless of co-morbidity status, HCWs should stay up to date with COVID-19 vaccination, including booster doses.