Objective: To evaluate the early predictive value of serum ferritin (SF), C-reactive protein (CRP), and D-dimer (D-D) in children with refractoryMycoplasma pneumoniae pneumonia (RMPP). Methods: A total of 107 children withMycoplasma pneumoniae pneumonia (MPP) were selected and classified into general group (GMPP group, n = 51) and refractory group (RMPP group, n = 56) according to treatment response and disease progression. The differences in serum SF, CRP, and D-D levels in the acute phase were compared between groups. Logistic regression analysis was adopted to screen the influencing factors of RMPP. Receiver operating characteristic (ROC) curve was utilized to evaluate the predictive efficiency of serum SF, CRP, D-D, and combined detection of the three indicators on RMPP. Results: There was no statistically significant difference in general information such as age, gender, and admission time between the two groups (P > 0.05). The RMPP group had a longer duration of fever and more involvement of lung lobes (P < 0.05). The levels of serum SF, CRP, and D-D in the RMPP group were higher than those in the GMPP group (P < 0.05). Multivariate Logistic regression revealed that the increases of SF, CRP, and D-D were the influencing factors of RMPP occurrence (P < 0.05). ROC curve analysis suggested that the area under the ROC curve (AUC) of the combination of SF, CRP, and D-D in predicting RMPP was 0.849, which was better than that of any single indicator (P < 0.05). Conclusion: Serum SF, CRP, and D-D levels are closely related to the disease severity and refractory progression of children with MPP. The three levels can be used as independent predictors of RMPP. Combined detection can provide an important basis for early warning of RMPP in children.