Abstract: Objective To explore the clinical characteristics of pleural effusion caused by Mycoplasma pneumoniae in children. Methods The clinical data from children with pleural effusion caused by Mycoplasma pneumoniae were retrospectively analyzed. Differences of clinical characteristics in children with pleural effusion caused by Mycoplasma pneumoniae infection and non-Mycoplasma pneumoniae infection were compared. Moreover, multiple logistic regression analysis was performed on the factors that were identified to have statistical differences in single factor analysis. Receiver operating characteristic (ROC) curve was performed and the diagnostic boundary value of each factor and the diagnostic accuracy of the regression model were calculated. Results There were statistical differences between children with pleural effusion caused by Mycoplasma pneumoniae infection and by non-Mycoplasma pneumoniae infection in age, white blood cell count, lactic dehydrogenase (LDH), levels of IgA and IgM, and the proportion of multiple nuclei, glucose and lactic acid (LAC) in pleural effusion, pleural thickening, and formation of fibrous separation (all P < 0.05). Multifactor logistic regression found the differences of age, levels of IgM and LDH, level of LAC are statistically different between the two groups (all P < 0.05), with their diagnostic boundary value of 3.92 years old, 1.29 g/L, 367 U/L and 4.02 mmol/L, respectively. ROC under the curve (AUC) was 0.887 (95% CI: 0.830-0.944, P < 0.001). Conclusion In children having pleural effusion caused by pneumonia of unknown pathogen, if their age is > 3.92 years, serum IgM > 1.29 g/L, LDH > 367 U/L and pleural effusion LAC < 4.02 mmol/L, Mycoplasma pneumoniae infection should be highly suspected.