ObjectiveTo explore the changes of serum Clara cell secretory protein 16(CC16), tumor necrosis factor-α (TNF-α), interleukin-6(IL-6) and pulmonary surfactant protein D (SP-D) in children with severe pneumonia. MethodsFrom March 2018 to March 2020, the children with pneumonia in Pediatrics Department of Maternity and Child Health Care Hospital of Zaozhuang were divided into severe group (n=104) and  mild group (n=100). Meanwhile 100 healthy children were included into healthy group. Serum levels of CC16, TNF-α, IL-6, SP-D were detected in the three groups. Respiratory mechanical parameters including work of breathing (WOB), airway resistance (RAW), lung dynamic compliance (Cdyn), and peak inspiratory pressure (PIP) were analyzed in the severe group at 1h, 72h after ventilator application and before withdrawal from the ventilator. The levels of serum CC16, TNF-α, IL-6 and SP-D in the three groups were compared by one-way analysis of variance. The levels of serum inflammatory factors and respiratory mechanical parameters in the severe group were compared at different time after ventilator application by repeated measurement analysis of variance. The correlation between the levels of serum CC16, TNF-α, IL-6,SP-D and respiratory mechanical parameters were analyzed by Pearson correlation analysis.ResultsThe levels of serum CC16, TNF-α, IL-6 and SP-D in severe group were (11.15±2.36)μg/L, (57.88±9.93)ng/L, (60.46±9.55)ng/L and (97.53±9.38)μg/L, respectively, while levels in mild group were (17.56±2.48)μg/L, (15.55±6.76)ng/L, (37.88±8.72)ng/L and (51.53±6.45)μg/L. The healthy group were (20.02±3.43)μg/L, (2.92±0.23)ng/L, (6.03±0.41)ng/L, (20.00±3.18)μg/L. The serum TNF-α, IL-6 and SP-D levels in severe group, mild group and healthy group decreased in turn, while the levels of serum CC16 in the three groups increased in turn （F=589.98, 482.76, 596.89, 45.46, all P＜0.05). Pearson analysis showed that serum CC16 level was negatively correlated with WOB, Raw and PIP (r=-0.70, -0.70, -0.69, all P＜0.05), serum TNF-α, IL-6, SP-D levels were positively correlated with  WOB, Raw and PIP （r=0.78,0.77,0.70，0.77,0.77,0.71，0.71,0.75,0.73, all P＜0.05）. Serum CC16 was positively correlated with Cdyn （r=0.81，P＜0.05）, serum TNF-α, IL-6, SP-D were negatively correlated with Cdyn （r=-0.79, -0.80, -0.80, all P＜0.05）.ConclusionThe levels of serum CC16, TNF-α, IL-6 and SP-D are related to severity of disease and respiratory function of children with severe pneumonia.