This study examines the rebound characteristics of respiratory infections, particularly *Mycoplasma pneumoniae*, following the relaxation of pandemic control measures in Shenzhen, China, from January to November 2023. The research involved testing patients for common respiratory viruses and *M. pneumoniae* using various methods, including antigen, nucleic acid amplification, and targeted next-generation sequencing (NGS). The results show a rapid rebound of SARS-CoV-2 followed by a slower rebound of *M. pneumoniae*, with a 5-month interval between their peaks. The hospitalization rate was higher for respiratory virus infections compared to *M. pneumoniae*, but the number of *M. pneumoniae* cases within 6 months posed a significant burden on healthcare services. Multivariate analysis revealed that *M. pneumoniae*-infected adults had more fatigue, comorbidities, and higher serum C-reactive protein levels, while children had a higher incidence of other respiratory pathogens detected by tNGS or pathogen-specific PCR, fever, and were more likely to be female. The study also found that 85% of *M. pneumoniae*-positive specimens had mutations at the 23rRNA gene, with 99.7% showing the A2063G mutation. Patients treated with doxycycline and fluoroquinolones showed faster defervescence compared to those treated with macrolides. The findings highlight the need for a review of treatment protocols for community-acquired pneumonia, especially in children, due to the high resistance rate of *M. pneumoniae*.This study examines the rebound characteristics of respiratory infections, particularly *Mycoplasma pneumoniae*, following the relaxation of pandemic control measures in Shenzhen, China, from January to November 2023. The research involved testing patients for common respiratory viruses and *M. pneumoniae* using various methods, including antigen, nucleic acid amplification, and targeted next-generation sequencing (NGS). The results show a rapid rebound of SARS-CoV-2 followed by a slower rebound of *M. pneumoniae*, with a 5-month interval between their peaks. The hospitalization rate was higher for respiratory virus infections compared to *M. pneumoniae*, but the number of *M. pneumoniae* cases within 6 months posed a significant burden on healthcare services. Multivariate analysis revealed that *M. pneumoniae*-infected adults had more fatigue, comorbidities, and higher serum C-reactive protein levels, while children had a higher incidence of other respiratory pathogens detected by tNGS or pathogen-specific PCR, fever, and were more likely to be female. The study also found that 85% of *M. pneumoniae*-positive specimens had mutations at the 23rRNA gene, with 99.7% showing the A2063G mutation. Patients treated with doxycycline and fluoroquinolones showed faster defervescence compared to those treated with macrolides. The findings highlight the need for a review of treatment protocols for community-acquired pneumonia, especially in children, due to the high resistance rate of *M. pneumoniae*.