High concentration of soluble E-cadherin (E-cad) was previously found in sera from Q fever patients. Here, BeWo cells which express a high concentration of E-cad were used as anin vitromodel to investigate the expression and function of E-cad in response to infection byCoxiella burnetii, the etiological agent of Q fever. Infection of BeWo cells withC.burnetiileads to a decrease in the number of BeWo cells expressing E-cad at their membrane. A shedding of soluble E-cad was associated with the post-infection decrease of membrane-bound E-cad. The modulation of E-cad expression requires bacterial viability and was not found with heat-inactivatedC.burnetii. Moreover, the intracytoplasmic cell concentration of β-catenin (β-cat), a ligand of E-cad, was reduced after bacterial infection, suggesting that the bacterium induces modulation of the E-cad/β-cat signaling pathway andCDH1andCTNNB1genes transcription. Finally, several genes operating the canonical Wnt-Frizzled/β-cat pathway were overexpressed in cells infected withC.burnetii. This was particularly evident with the highly virulent strain ofC.burnetii, Guiana. Our data demonstrate that infection of BeWo cells by liveC.burnetiimodulates the E-cad/β-cat signaling pathway.