Following the COVID-19 pandemic, infections with Mycoplasma pneumoniae (M. pneumoniae) have resurged globally. However, post-pandemic changes in clinical phenotypes, severity, and extrapulmonary manifestations remain poorly characterised in pediatric populations. This study aimed to characterise the clinical spectrum, severity patterns, and phenotypic differences of M. pneumoniae infection in hospitalised children following the COVID-19 pandemic, and to identify risk factors for critical illness in a multicenter cohort. This multicenter retrospective study included 400 hospitalised children with confirmed M. pneumoniae infection across 20 tertiary pediatric centres in Turkey between July 2021 and July 2024. Demographic, clinical, laboratory, and radiologic features were analysed. Groups were compared by age, pulmonary versus extrapulmonary phenotypes, and disease severity. Multivariate logistic regression was used to identify predictors of critical illness. A total of 400 hospitalised children with confirmed M. pneumoniae infection were included in the study, of whom 212 (53%) were male. The median age was 88 months (interquartile range [IQR]: 48–124 months). Underlying conditions were present in 110/400 (27.5%) patients, with asthma/reactive airway disease, neurological disorders, and hematologic/oncologic disorders being the most common comorbidities. Pneumonia was identified in 303/400 (75.8%) patients. Extrapulmonary organ involvement was observed in 79/400 (19.8%) patients, predominantly affecting the hematologic and neurologic systems. Critical illness criteria were met in 216/400 (54%) patients. Oxygen support was required in 145/400 (36.3%), and ICU admission occurred in 36/400 (9%). Children ≥ 5 years were more likely to present with lobar pneumonia, while those < 5 years had higher rates of gastrointestinal symptoms without severe inflammation. Fever, cough, and CRP elevation were strongly associated with pulmonary disease (p < 0.001). Elevated neutrophil count independently predicted critical illness (OR: 1.002; 95% CI: 1.000–1.004; p = 0.046). Treatment varied by phenotype: clarithromycin was used more frequently in pneumonia cases, while azithromycin, corticosteroids, and IVIG were more commonly used in extrapulmonary cases. Conclusion: In the post-COVID-19 era, pediatric M. pneumoniae infections show increased severity and clinical diversity. Distinct phenotypes and age-related patterns underscore the need for tailored care. Prospective studies with resistance and immune profiling are needed to inform future management strategies. (Table presented.)