Interleukin 33 (IL‐33) and soluble form of ST2 (sST2) are involved in inflammation. This study aimed to assess the role of serum IL‐33 and sST2 in neonates with HCMV infection. The concentration of serum IL‐33 and sST2 in 20 patients and 16 healthy controls were measure by enzyme‐linked immune‐sorbent assay (ELISA). The clinical and laboratory data were described. Our results showed serum sST2 and IL‐33 levels were significantly higher in the HCMV group than the control group. Significant positive correlation was observed between sST2 and IL‐33 (r = 0.518, P = 0.001). Furthermore, there was a positive, moderate, and statistically significant correlation between sST2 and ALT levels in the control and HCMV groups (r = 0.579, P = 0.007; r = 0.66, P = 0.005, respectively). The AUC of sST2 and IL‐33 was found to be 0.822 and 0.867 respectively. Further, at a cut‐off value of 1823.4 ng/mL, sST2 gave 65% sensitivity and 93.7% specificity. Similarly, IL‐33 gave 95% sensitivity and 68.7% specificity at a cut‐off value 2.04 pg/mL. The Youden index of sST2 and IL‐33 was found to be 0.587 and 0.637, respectively. In conclusion, this study revealed that sST2 and IL‐33 have great potential to be used as biomarkers for early screening and indicate liver damage for HCMV patients in future after validation in large cohort study. [ABSTRACT FROM AUTHOR]