Background: The outbreak of the novel Coronavirus Disease (COVID-19) was declared a pandemic by the World Health Organization on March 2020. Studies show that healthcare workers from previous pandemics (A/H1N1 influenza; severe acute respiratory syndrome, SARS), have experienced high levels of stress, anxiety and low mood with negative psychological impacts sustained after one year. This paper aims to identify factors affecting mental health outcomes of healthcare workers during Coronavirus Disease (COVID-19) pandemic at Cardinal Santos Medical Center. Methods: This is a cross-sectional study of factors affecting mental health outcome of healthcare workers with direct contact to a patient with confirmed or suspected case Coronavirus Disease (COVID-19) at Cardinal Santos Medical Center from March 2020 to September 2020. The severity of mental health outcome in terms of depression, anxiety and distress were measured using the 9-item Patient Health Questionnaire, the 7-item Generalized Anxiety Disorder scale, and the 22-item Impact of Event Scale–Revised, respectively. Binomial multiple logistic regression model was used to identify the factors associated with mental health outcome. Results: A total of 172 healthcare workers were included in this study. Prevalence of depression, anxiety and distress symptoms among all healthcare workers were 57%, 47.7%, 65.1%, respectively. After multivariate analysis, age and living with a family with comorbidities are significantly associated with depression and anxiety. Healthcare workers aged 31 years and above are 70% less likely to have depression symptoms (OR 0.278, CI 95%, 0.11-0.72 p=0.008 and OR 0.273, CI 95%, 0.12-0.61, p=0.002). Those living with relatives with comorbidities are 2.7 times more likely to experience depression symptoms (OR 2.731, CI 95%, 1.36-5.5, p=0.005). Healthcare workers age 31-40 years has 80% less likely to experience anxiety symptoms (OR 0.212, CI 95%, 0.09-0.5, p<0.001), and those age 41 and above have 73% less likely to have anxiety symptoms (OR 0.37, CI 95%, 0.14-0.98, p<0.045). Those living with relatives with comorbidities are 2.9 times more likely to have anxiety symptoms (OR 2.889, CI 95%, 1.46-5.73, p=0.002). Level of knowledge on COVID-19 among health care workers significantly differs across severity but has no significant association with prevalence of depression. No factors were associated with distress symptom. Conclusion: Emotional strain by health care workers during pandemic can cause adverse outcomes not only for individual wellbeing, but also for patient care and the healthcare system. Cognizant of high rates of depression, anxiety and distress among our younger health care workers living with relatives with comorbidities during this time will be a challenge to both hospital management and the government to establish and/or improve existing programs to promote mental wellbeing and address their mental health needs. These programs should be readily available and accessible to healthcare workers seeking psychological support. Psychological stress can accumulate over time and have an impact later in the outbreak, including posttraumatic stress disorder (PTSD), which should be investigated in future studies. Funding Statement: No Funding. Declaration of Interests: No conflict of interest. Ethics Approval Statement: The clinical protocol was reviewed and approved by the Research Ethics Review Committee (RERC) of Cardinal Santos Medical Center. The researchers ensured that all information gathered were kept strictly confidential and used solely for the purpose of the study. An informed consent was given is attached together with the questionnaire.