BackgroundHomelessness is a more complex problem than the simple lack of a place to live. Homeless people (HP) often suffer from poor health and premature death due to their limited access healthcare, and are also deprived of basic human and social rights. The study protocol described here aims to evaluate the complex relationship between homelessness and health, and identify the barriers and facilitators that impact access to healthcare by HP.MethodsThis is a mixed-methods study that uses an explanatory sequential design. The first phase will consist of a cross-sectional study of 300 HP. Specific health questionnaires will be used to obtain information on health status, challenges during the COVID-19 pandemic, self-reported use of healthcare, diagnoses and pharmacologic treatments, substance abuse (DAST-10), diet quality (IASE), depression (PHQ-9), and human basic needs and social support (SSQ-6). The second phase will be a qualitative study of HP using the “life story” technique with purposive sampling. We will determine the effects of different personal, family, and structural factors on the life and health status of participants. The interviews will be structured and defined using Nussbaum's capability approach. DiscussionIt is well-known that HP experience poor health and premature death, but more information is needed about the influence of the different specific social determinants of these outcomes and about the barriers and facilitators that affect the access of HP to healthcare. The results of this mixed methods study will help to develop global health strategies that improve the health and access to healthcare in HP.