The effect of Saccharomyces boulardii on the immune system was evaluated, comparing germ‐free Swiss/NIH mice monoassociated with the probiotic with germ‐free mice. Saccharomyces boulardii colonized the gut of germ‐free mice and survived the gastrointestinal conditions. An increase in sIgA production, both total and anti‐S. boulardii, was observed in the intestinal contents of monoassociated mice when compared with germ‐free controls. The number of Küpffer cells was significantly higher in monoassociated mice than in germ‐free controls. In S. boulardii‐monoassociated mice, clearance of Escherichia coli B41 was higher than in germ‐free controls. TNF‐α, IFN‐γ and IL‐12 serum levels were higher at earlier time points in monoassociated mice when compared with germ‐free mice. These results show that the yeast S. boulardii modulates the host immune responses. This effect may be of interest for improving the resistance to enteropathogenic bacterial infections.