This cohort study evaluated the associations of C-reactive protein-neutrophil to lymphocyte ratio (C-NLR) and lymphocyte-CRP ratio (LCR) with refractory Mycoplasma pneumoniae pneumonia (RMPP), and the predictive values of C-NLR and LCR for RMPP and prolonged fever in children based on 389 children with MPP. The associations of NLR, C-NLR, and LCR with RMPP and prolonged fever were evaluated by logistic regression analysis. C-NLR was correlated with an increased risk of RMPP in children [odds ratio (OR) = 3.459, 95% confidence interval (CI): 1.598–7.491]. A higher risk of RMPP was identified in the C-NLR > 29.9 group (OR = 2.885, 95% CI: 1.599–5.203). LCR > 1584.2 was associated with a decreased risk of RMPP (OR = 0.500, 95% CI: 0.282–0.887). Increased risk of prolonged fever in children was identified with the increase of C-NLR (OR = 5.913, 95% CI: 2.335–14.972) or NLR (OR = 2.413, 95% CI: 1.689–3.446). The AUCs of C-NLR, LCR, and NLR for predicting RMPP were 0.630, 0.623, and 0.608, respectively. In conclusion, C-NLR was associated with increased RMPP risk in children and had good value for predicting RMPP and prolonged fever in children.