Background: To investigate the clinical relevance of cytokine levels in assessment of the severity of mycoplasma pneumoniae pneumonia (MPP) in children., Methods: A retrospective study was conducted on 150 pediatric cases of MPP admitted to a local hospital in China from November 1, 2022 to October 31, 2023. These MPP cases were divided into mild (n=100) and severe (n=50) groups according to the severity of the disease. Cytokine levels, including Interferon-γ (IFN-γ), Tumor Necrosis Factor-α (TNF-α), C-reactive protein (CRP), Interleukin-6 (IL-6), Interleukin-2 (IL-2), and D-Dimer (D-D), were compared between the two groups. The diagnostic efficacy of each cytokine in assessing the severity of MPP was analyzed through Receiver Operating Characteristic (ROC) curves, and correlation between cytokine levels and disease severity was assessed using Pearson's correlation coefficient., Results: The IL-2 level was significantly lower, while TNF-α, IL-6, and IFN-γ levels were significantly higher in the severe group compared to the mild group (all P<0.05). TNF-α, IFN-γ, IL-2, IL-6, CRP, and D-D were identified as factors influencing the severity of MPP (all P<0.05). The ROC curve analysis showed that the areas under the curve (AUCs) of TNF-α, IL-2, IL-6, IFN-γ, CRP, and D-D were 0.864, 0.692, 0.874, 0.949, 0.814, and 0.691, respectively (all P<0.001), indicating their diagnostic value in assessing the severity of MPP. There exists a positive correlation between IL-2 and the percentage of normal lung density on Computed Tomography (CT) scan (P<0.05), while TNF-α, IL-6, IFN-γ, CRP, and D-D showed negative correlations with the percentage of normal lung density (P<0.05)., Conclusion: Cytokines such as TNF-α, IL-2, IL-6, IFN-γ, CRP, and D-D are aberrantly expressed in children with MPP and are associated with the severity of the disease. These cytokines have high diagnostic value and can serve as reference indicators for clinical, especially prognostic assessment of the severity of (pediatric) MPP., Competing Interests: None., (AJTR Copyright © 2024.)