Background: Mycoplasma bovis is a causative agent of disease in cattle causing many clinical conditions. Currently there are no commercial M. bovis vaccines in Europe and treatment is difficult with decreased antimicrobial susceptibility of M. bovis field isolates. Using an M. bovis calf infection model the effectiveness of enrofloxacin given alone; in combination with flunixin meglumine, a nonsteroidal anti inflammatory drug; and a group with an additional treatment of pegbovigrastim, an immunostimulator, was evaluated. Enrofloxacin given alone stimulated a strong immune response, reduced the clinical manifestation and lung lessions of the M. bovis infection. In contrast the combination therapy appeared ineffective. In this experiment enrofloxacin given alone appeared to be the most effective treatment of the M.bovis affected calves, whereas co-administration with flunixin meglumine, and pegbovigrastim was not beneficial in this trial.