Mycoplasma pneumoniae (M. pneumoniae), as one of the susceptible pathogens during childhood, may lead to severe mycoplasmal pneumonia and affect platelet fluctuations. We prospectively collected data on persistent/chronic ITP children who were infected with M. pneumoniae infection from August 2023 to December 2023. There were 64 patients (40 males) with a median age of 7.08 years (range 4.30 to 9.76) enrolled in this study. Overall, 33 (51.6%) children received TPO-RAs therapy and 31 (48.4%) received other treatments. The impact of M. pneumoniae infection on platelet count is bidirectional, but thrombocytopenia remains predominant. During M. pneumoniae infection, platelet changes in the TPO-RA group were higher than in the non-TPO-RA group. Thrombocytosis was observed in 6 patients (5 in the TPO-RA group vs. 1 in the non-TPO-RA group). Rescue treatment was implemented in 18 patients (7 in the TPO-RA group vs. 11 in the non-TPO-RA group). Monitoring platelets should be strengthened during M. pneumoniae infection.