Background: Levels of anti-inflammatory cytokines in blood have a positive relationship with congenital heart disease (CHD). We sought to assess the difference in serum cytokines levels between children with and without CHD. Methods: We recruited 60 patients with CHD and 30 healthy children, from 2013 to 2014. Patients with primary pulmonary hypertension; metabolic diseases; renal, endocrine, and chronic inflammatory diseases; fever; infection in the preceding 3 weeks; and malnutrition were excluded. Participants’ demographic data were measured, and their cardiac diseases were diagnosed via echocardiography. Serum levels of tumor necrosis factor (TNF)-α , interleukin (IL)-6, and IL-18 were measured via ELISA. Results: Mean age of the participants was 4. 28 ± 3. 44, 3. 12 ± 3. 87, and 3. 30 ± 3. 61 years in the cyanotic, acyanotic, and control groups, respectively (p value = 0. 414). Mean values of TNF-α (p value < 0. 001), IL-6 (p value < 0. 001), IL-18 (p value = 0. 030), right ventricular pressure (p value < 0. 001), and pulmonary pressure (p value = 0. 015) were higher in the case group, while the BMI was higher in the controls (p value < 0. 001). Mean values of TNF-α (p value < 0. 001), IL-6 (p value < 0. 001), and right ventricular pressure (p value < 0. 001) were significantly higher in the cyanotic children, whereas the BMI was higher in the controls (p value < 0. 001). Levels of TNF-α and IL-6 had significant correlations with right ventricular pressure. Conclusion: The present study showed a differed serum cytokines levels between children with and without CHD.