Mycoplasma pneumoniaeis the most common bacterial cause of pneumonia in children hospitalised for community-acquired pneumonia. Prevention of infection by vaccines may be an important strategy in the presence of emerging macrolide resistantM. pneumoniae.However, knowledge of immune responses toM. pneumoniaeis limited, complicating vaccine design. We therefore studied the antibody response duringM. pneumoniaeinfection and asymptomatic carriage.In a nested case-control study (n=80) ofM. pneumoniaecarriers and matched controls we observed that carriage byM. pneumoniaedoes not lead to a rise in either mucosal or systemicM. pneumoniae-specific antibodies, even after months of persistent carriage. We replicated this finding in a second cohort (n=69) and also found that duringM. pneumoniaecommunity-acquired pneumonia, mucosal levels ofM. pneumoniae-specific IgA and IgG did increase significantly.In vitroadhesion assays revealed that high levels ofM. pneumoniae-specific antibodies in nasal secretions of paediatric patients prevented the adhesion ofM. pneumoniaeto respiratory epithelial cells.In conclusion, our study demonstrates thatM. pneumoniae-specific mucosal antibodies protect against bacterial adhesion to respiratory epithelial cells and are induced only duringM. pneumoniaeinfection and not during asymptomatic carriage. This is strikingly different from carriage with bacteria such asStreptococcus pneumoniaewhere mucosal antibodies are induced by bacterial carriage.