Introduction: Stigma develops during outbreaks such as the COVID-19 pandemic due to the human fear that arises from the anxiety about a disease of an unknown etiology, with the associated detrimental consequences on both the individual and society. This study was conducted to assess if knowledge about COVID-19, attitude, practice and behavior regarding preventive measures against COVID-19, fear, and anxiety towards COVID-19 will affect the level of stigma and evaluate the mediating effect of fear, anxiety, and diagnosis of COVID-19 on stigma. Methods: A cross-sectional online survey conducted between December 20, 2020, and January 05, 2021, enrolled 405 participants recruited from the Lebanese population. Two scales were created and adapted to the Lebanese context to measure the current stigma (stigma discrimination scale, self-stigma scale) toward COVID-19. Results: More than half of the sample had moderate to severe stigma discrimination (62%) and self-stigma (65.9%). The multivariable analysis showed that higher fear of COVID-19 scale (Beta = .143) was significantly associated with a higher stigma discrimination scale. Whereas, higher knowledge score (Beta = −.153) was significantly associated with a lower stigma discrimination scale. Fear of COVID-19, anxiety from COVID-19, being diagnosed with COVID-19, and having a family member with COVID-19 partially mediated the association between knowledge and stigma discrimination scale. No mediation effect of fear and anxiety scale was found between the knowledge and self-stigma score. Conclusion: Our main findings indicate that a considerable proportion of the Lebanese population has stigma discrimination behaviors toward COVID-19 patients and that those who were infected with the virus experienced COVID-19-related stigmatization.