The COVID-19 (coronavirus disease 2019) pandemic is associated with far-reaching psychological consequences, such as anxiety. The incidence and severity of this anxiety depend on several individual, family and social factors that need to be identified and planned for effective interventions. One of these factors is health literacy (HL). The aim of this study was to determine the relationship between HL and demographic characteristics with COVID-19 anxiety in adults living in Iran at the time of coronavirus outbreak. This is a descriptive and correlational study conducted in Iran in 2021. Convenience and snowball sampling methods were used, and as the result, the number of samples reached to 560. Data were collected online through the demographic questionnaire, COVID-19 anxiety scale (CAS) and health literacy questionnaire for adults (HLQ for adults). Data were analyzed using Amos 26, SPSS 26 software and structural equational modeling (SEM) based on covariance. Significance level in this study was considered 0.05. The results of this study showed that the fit of the modify model is confirmed and HL explains 54% of the changes in anxiety in the model (β ¼ -0.709). The variables of gender, history of chronic disease, positive history of COVID 19 and receiving social support have a moderating role in the relationship between HL and COVID-19 anxiety. Due to the great predicting role of HL in COVID-19 anxiety, it is recommended that programs be developed and implemented during the outbreak of the disease by experts and the public health policy makers to increase HL in physical and mental dimensions.