Childhood obesity represents a worldwide concern as many countries have reported an increase in its incidence, with possible cardiovascular long-term implications. The mechanism that links cardiovascular disease to obesity is related to low-grade inflammation. We designed this study to investigate the diagnostic utility of inflammatory indices (NLR, neutrophil-to-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio; SII, systemic immune-inflammation index; SIRI, systemic inflammation response index) in obese children with metabolic syndrome (MetS) and their relationship with cardiometabolic risk biomarkers, such as the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), triglyceride-to-high-density lipoprotein cholesterol (TG:HDL-C), and non-high-density lipoprotein cholesterol (non-HDL-C). A total of 191 obese children from one large Romanian reference center was included in the study. Patients were classified in two groups according to the presence (MetS group) or absence (non-MetS group) of metabolic syndrome. According to our results, the SII index proved to have diagnostic value in distinguishing MetS patients among children with obesity (AUC = 0.843, a sensitivity of 0.83, and a specificity of 0.63). Furthermore, the SII was positively associated with cardiometabolic risk biomarkers (HOMA-IR,p< 0.001; TG:HDL-C,p= 0.002; non-HDL-C,p= 0.021), highlighting its possible role as an additional measure of cardiometabolic instability in obese children.