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Coronavirus disease 2019 (COVID-19) infection has become a clinical threat to healthy people as well as immunocompromised patients and those with pre-existing chronic diseases around the world. This study, which used a cross-sectional correlational design, aimed to assess the levels of fear and health anxiety and to investigate their predictors during the current outbreak of COVID-19 in immunocompromised and chronic disease patients in Saudi Arabia. Sociodemographic and clinical data, fear of COVID-19, and health anxiety measurements were collected by online surveys from June 15 to July 15, 2020. Univariate and multiple linear regression analysis was used to identify predictors. A total of 1,030 patients in 13 provinces in Saudi Arabia completed the questionnaire. A significant number of patients with chronic diseases experienced considerable levels of fear and anxiety during the COVID-19 outbreak. It was found that 21.44% of participants met the criteria for anxiety cases, and 19.4% were considered borderline anxiety cases. In regression analysis, significant predictors of fear and health anxiety were female gender, lower education, middle-aged, divorced or widowed, receiving immunosuppressants, type of chronic disease (Crohn's disease, hypertension, and cardiovascular diseases), and media use as a source of knowledge about COVID-19. Immunocompromised and chronic disease patients are vulnerable to fear and anxiety during epidemic infectious diseases such as COVID-19. Optimizing this population's compliance with appropriate infection prevention and control strategies is crucial during the infectious outbreaks to ensure their safety, to decrease the risk of infection and serious complications, and reduce their fear and health anxiety. Effective positive psychological interventions and support strategies also need to be immediately implemented to increase psychological resilience and improve the mental health of these patients. Due to the COVID-19 outbreak, chronic disease patients in Saudi Arabia need special attention from health authorities, policymakers, and healthcare professionals to manage maladaptive forms of health anxiety and fear., Competing Interests: The authors have declared that no competing interests exist.