Patients with hemodialysis face various problems with self-care behavior. Therefore, these patients need to control and manage adherence to enhance self-care, especially during the COVID-19 pandemic, which has particularly high morbidity in the elderly and co-morbid peoples. Self-efficacy was identified as a number of psychological factors that improve adherence and treatment outcomes among hemodialysis patients. This study aimed to investigate self-efficacy among patients with hemodialysis during the COVID-19 pandemic. A comparative descriptive research design was used to conduct the study. A convenience sample of 95 hemodialysis patients (male and females) was selected from Port-Said city, Egypt, and 115 hemodialysis patients (male and females) were selected from Saudi Arabia. Data collection included a structured interview with three parts assessing socio-demographic characteristics, anthropometric measurements, and self-efficacy. This study revealed a statistically significant difference between Egyptian and Saudi hemodialysis patients, mainly in the main score and levels of self-efficacy (p=0.001). There is a significant relationship between socio-demographic characteristics and chronic disease self-efficiency among Egyptian hemodialysis patients in terms of sex, age, marital status, work, and level of education.