Abstract: Objective To investigate the levels of creatine kinase (CK-MB), brain natriuretic peptide (BNP), and neuropeptide Y (NPY) in severe pneumonia pediatric patients combined with heart failure (HF). Methods Pneumonia pediatric patients admitted from December 2010 to December 2014 had been enrolled and divided into pneumonia group (P) (n=32), severe pneumonia group (SP) (n=20) and severe pneumonia combined HF group (HF) (n=36). Twenty healthy children served as control group (C). Serum level of CK-MB was detected by enzyme rate method and were measured by ELISA. BNP and NPY were measured again during the recovery period in 18 cases in HF group. Results The serum levels of CK-MB, BNP and NPY were significantly different among the four groups, (F=25.19 ~ 277.94, P <0.01). The serum levels of CK-MB, BNP and NPY were significantly higher in HF group than in SP, P and C group (P<0.05). The serum level of CK-MB was significantly higher in SP group than that in P and C group (P <0.05) and there was no difference between P and C group (P>0.05). The serum levels of BNP and NPY were not statistically significant between SP and P and C group (all P> 0.05). In HF group, the serum levels of CK-MB, BNP, and NPY were significantly decreased in 18 cases after treatment. The serum level of BNP was positively correlated with CK-MB and NPY (r = 0.681, 0.525, all P<0.01) and the NPY and CK-MB levels were also positively correlated (r=0.545, P <0.01). Conclusions The Detection of the serum levels of CK-MB, BNP and NPY can help diagnose severe pneumonia combined with HF. The BNP maybe the most sensitive indicator.