Background: Chronic disease management offers problems to human well-being and the long-term viability of healthcare systems, and promoting self-care is seen as a critical issue for people with chronic illnesses. Aim: This study aimed to investigate the relationship between illness perception and self-care maintenance among patients with chronic disease. Subjects and Method: Design: descriptive correlational research design was used in this study. Setting: The study was conducted at the outpatient clinics, hospitals, and primary healthcare centers affiliated to the Ministry of Health in Port Said City. Sample: A convenience sample of 1,005 patients were included in the study. Tools: Three tools were used in this study: a patient interview questionnaire, a self-care maintenance scale, and a brief illness perception scale. Results: This study's results found a significant relationship between self-care maintenance and chronic disease patient perception about their illness regarding all dimensions with a p-value that ranged from 0.000 to 0.05 except for the dimension related to personal control and emotion. Conclusion: Self-care was a significant relationship to disease perception among study patients with chronic conditions. Furthermore, age, education level, work, the current diagnosis, and previous hospitalizations were found to be significantly linked with sustaining self-care and illness perception among chronic illness patients. Recommendations: Developing self-care programs aimed at improving the self-care behaviors of people with chronic illnesses taking into consideration the study associated factors. Develop nursing interventions and strategies to raise self-care maintenance and awareness regarding self-care among chronic disease patients.