Abstract: Objectives: The current study explores the level of perceived social stigma and associated psychological challenges among healthcare workers during the second wave of the COVID-19 pandemic in Egypt. Methods: This was a cross-sectional study of 150 healthcare workers at Cairo University hospitals that were confirmed positive for COVID-19 infection. Participants were interviewed for assessment of perceived COVID-19-related stigma and associated psychological symptoms using the Patient Health Questionnaire for depression, the Generalized Anxiety Disorder Assessment for anxiety, and the Post-Traumatic Stress Disorder Checklist for post-traumatic stress symptoms. Results: Two-thirds of participants perceived moderate-to-severe COVID-19-related stigma. Depression, anxiety, and post-traumatic stress symptoms were observed at varying levels in 58.0%, 38.0%, and 11.3% of participants, respectively. Female sex and occupation as a nurse were significantly associated with the total perceived COVID-19-related stigma score. COVID-19-related stigma perception significantly correlated with depression, anxiety, and post-traumatic stress. Conclusion: Perceived social stigma prevails among healthcare workers and is associated with numerous psychological disturbances.