Background: Hospital waste disposal workers are vulnerable subgroup of front-line health care workers, and are at a significant danger of catching any infection. Objective: The purpose of this study was to determine psychological problems among hospital waste disposal workers during the outbreak of COVID-19. Methods: A comparative cross-sectional study was conducted among 120 frontline hospital waste disposal workers handling any type of medical waste during COVID-19 versus 120 non-frontline academic departments' waste disposal workers. Data was collected using semi- structured questionnaire covering sociodemographic and occupational characteristics, the clinical picture of COVID-19 infection, COVID-19 related knowledge, and psychological problems including Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire (PHQ-9) and General Health Questionnaire (GHQ). Results: One hundred and twenty frontline hospital waste disposal workers versus 120 academic workers showed no significant difference regarding demographic factors. As regard mental disorders, frontline waste disposal workers experienced anxiety and depression more than other group (P-value<0.001). Binary logistic regression analysis for different factors affecting existence of anxiety and depression, showed that higher education level, 24 working hours/day, more than 10 shifts per month and good COVID-19 related knowledge were risk factors for anxiety, depression, social dysfunction and loss of confidence. On the other side, age ≥32 years was a protective factor for both anxiety (AOR 0.13) and depression (AOR 0.06) while usage of Personal Protective Equipment (PPE) (AOR 0.006) was a protective factor for social dysfunction & loss of confidence. Conclusion: Frontline hospital waste disposal workers had a risk of psychological problems during outbreaks.