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© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)., Students with chronic conditions (CC) tend to experience several barriers in terms of their school participation and performance. Therefore, the present study aims to explore the factors related to the time of diagnosis of CC (recent/non-recent), the barriers to participation and academic success (health condition, people's attitude towards CC and school physical environment), the physical and mental health (physical/psychological symptoms and concerns) and school-related variables (relationship with teachers and peers), regarding the school participation of first-year students with CC. This work is part of the HOUSE-Colégio F3 Project, University of Lisbon, which includes 1143 first-year university students from 17 Faculties and Institutes of the University of Lisbon. In this specific study, only the subsample of 207 students with CC was considered, 72.4% of which were female, aged between 18 and 54 years (M = 20.00; SD = 4.83). The results showed that students with a recent diagnosis of CC and students with school participation affected by the CC were those who presented more negative indicators regarding barriers to school participation, physical and mental health, and school-related variables. A greater impact of CC in terms of school participation was associated with having a recent diagnosis, with people's attitude towards CC and with the health condition as barriers, with more psychological symptoms and worse relationships with teachers and peers. This is a relevant message for the organization of health services for students with CC at the beginning of their university studies, especially since they are often displaced from home and managing their health conditions alone (in many cases, for the first time)., Ana Cerqueira—Foundation for Science and Technology (FCT) Grant (SFRH/BD/148403/2019). Fábio Botelho Guedes—Foundation for Science and Technology (FCT) Grant (SFRH/BD/148299/2019).