: The current study aims at evaluating the effect of the oral administration of Lactobacillus casei CERELA (CRL) 431 on parameters implicated in inflammation-coagulation interaction using a model of acute inflammation induced by lipopolysaccharide (LPS) in mice. Six-week-old Balb/c mice were treated with L. casei for 5 consecutive days. Then treated and untreated mice received an LPS injection (L. casei + LPS and LPS groups, respectively). Liver and kidney were removed, blood samples were obtained, and hemostatic and inflammatory parameters were evaluated at different times post LPS injection. Preventive L. casei administration induced a significant decrease in proinflammatory TNF-α and IL-6 cytokines by decreasing tissue factor expression in liver and kidney. Moreover, the lower expression of tissue factor in the L. casei + LPS group led to a lower activation of the coagulation system, which was observed by the fast systemic restoration of factors VII and V coagulation factors and antithrombin levels. This study highlights the capacity of L. casei to modulate the hemostatic unbalance in an acute endotoxemia model. Our findings showed the ability of L. casei CRL 431 to regulate the immuno-coagulative response. This fact could be helpful to propose new adjunctive strategies addressed to the restoration of physiological anticoagulant mechanisms in sepsis patients.