Background. Although Lactobacillus casei Shirota (LcS) can benefit the immune status, the effects of LcS in the immune/inflammatory responses of marathon runners has never been evaluated. Therefore, here we evaluated the effect of daily ingestion of fermented milk containing or not LcS in the systemic and upper airway immune/inflammatory responses before and after a marathon. Methods. Forty-two male marathon runners ingested a fermented milk containing 40 billion of LcS/day (LcS group, n = 20) or placebo (unfermented milk, n = 22) during 30 days pre-marathon. Immune/inflammatory parameters in nasal mucosa and serum, as well as concentrations of secretory IgA (SIgA) and antimicrobial peptides in saliva, were evaluated before and after fermented milk ingestion, immediately, 72 h, and 14 d post-marathon. Results. Higher proinflammatory cytokine levels in serum and nasal mucosa, and also lower salivary levels of SIgA and antimicrobial peptides, were found immediately post-marathon in the placebo group compared to other time points and to LcS group. In opposite, higher anti-inflammatory levels and reduced neutrophil infiltration on nasal mucosa were found in the LcS group compared to other time points and to the placebo group. Conclusion. For the first time, it is shown that LcS is able to modulate the systemic and airways immune responses post-marathon.