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International audience; Background Knowledge of the long-term effects of soccer training on hematological, hormonal, inflammatory, and muscle damage markers and physical performance may help to better design strength and conditioning programs for performance development and injury prevention for the individual player and the team. Objectives The aim of this systematic review was to summarize and discuss evidence on the long-term effects of soccer training on selected hematological, hormonal, inflammatory, and muscle damage markers and physical performance in elite and professional soccer players. A second goal was to investigate associations between selected physiological markers and measures of performance. Methods Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, a systematic literature search was conducted in four electronic databases (PubMed, ISI Web of Knowledge, Web of Science, and SPORTDiscus) from inception until August 2020 to identify articles related to soccer training effects. To be included in this systematic review, studies had to examine male elite (national level) and/or professional (international level) soccer players aged > 17 years and a soccer training period > 4 weeks, and report outcomes related to hematological, hormonal, inflammatory, muscle damage, and performance markers. Results The search syntax initially identified 2420 records. After screening titles, abstracts, and full texts, 20 eligible studies were included in this systematic review, with training durations lasting between 4 and 18 weeks in 15 studies, around 6 months in four studies, and around 1 year in one study. Effects of long-term soccer training revealed parameter-specific increases or decreases in hematological, hormonal, inflammatory, and muscle damage markers and physical performance. Two studies showed a moderate increase in hematological markers such as hemoglobin (effect size [ES] = 0.67-0.93). Parameter-specific changes were noted for hormonal markers in the form of increases for total testosterone (ES = 0.20-0.67) and free testosterone (FT) (ES = 0.20-0.65) and decreases for cortisol (ES = - 0.28 to - 1.31). Finally, moderate to very large increases were found for muscle damage markers such as creatine kinase (ES = 0.94-6.80) and physical performance such as countermovement jump (CMJ) height (ES = 0.50-1.11) and squat jump (SJ) height (ES = 0.65-1.28). After long-term periods of soccer training, significant positive correlations were found between percentage change (Delta%) in FT and Delta% in CMJ height (r = 0.94; p = 0.04) and between Delta% in total testosterone/cortisol (TT/C) ratio and Delta% in SJ (r = 0.89; p = 0.03). Conclusions Findings suggest that long-term soccer training induces increases/decreases in hematological, hormonal, inflammatory, and muscle damage markers and physical performance in male elite and professional soccer players. These fluctuations can be explained by different contextual factors (e.g., training load, duration of training, psychological factors, mood state). Interestingly, the observed changes in hormonal parameters (FT and TT/C) were related to vertical jump performance changes (e.g., CMJ and SJ). Anabolic hormones and TT/C can possibly be used as a tool to identify physical performance alteration after long-term soccer training.