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Viviane Soares,1 Ivan Silveira de Avelar,2 Patrícia Espíndola Mota Venâncio,1 Deise AA Pires-Oliveira,1 Pedro Henrique de Almeida Silva,1 Amanda Rodrigues Borges,1 Gustavo Paz Estevez Ferreira Fonseca,3 Matias Noll4 1Programa de Pós-Graduação em Movimento Humano e Reabilitação, Centro Universitário de Anápolis UniEVANGÉLICA, Anápolis, Goiás, Brazil; 2Faculdade da Polícia Militar, Curso de Educação Física, Goiania, Goiás, Brazil; 3Hospital Geral de Goiânia, Goiânia, Goiás, Brazil; 4 Instituto Federal Goiano (IF Goiano), Department of Public Health, Ceres, Goiás, BrazilCorrespondence: Viviane SoaresCentro Universitário de Anápolis, Avenida Universitária Km 3,5, Cidade Universitária, Anápolis, Goiás 75083-515, BrazilTel +55 62 3310-6688Email ftviviane@gmail.comBackground: Interleukin 6 (IL-6) has an inflammatory effect, and its concentration in serum increases during exercise. However, no studies have assessed acute changes in IL-6 concentration after consecutive days of extreme and long-term exercise.Objective: This study aimed to assess acute changes in serum IL-6 concentration during four days of long-distance walking.Methods: This prospective observational study assessed 25 athletes (aged 44.8 ± 9.1 years), who covered a total of 251 km in four days. Blood samples were collected daily to assess serum IL-6 concentrations. Repeated-measures analysis of variance (with Bonferroni’s post hoc test) and the Kruskal–Wallis H-test (with Dunn’s post hoc test) were used to investigate the differences between the measures.Results: The serum IL-6 concentrations were higher on the four days of walking (1st day: 26.8 ± 14.8; 2nd day: 14 ± 7.4; 3rd day: 9.4 ± 10.8; 4th day: 4.5 ± 0.2 pg/mL) when compared to pre-walk values (pre-walk: 2.2 ± 2.1 pg/mL; p < 0.001). On the first day, there was a tenfold increase compared to the pre-walk value.Conclusion: The inflammatory response increased the serum concentration of IL-6 after four days of exercise. With the passing of days, there were reductions but not to baseline values.Keywords: exercise, long-distance walk, inflammation, biomarker, interleukin-6, athletes