Aim: The main objective of the study was to determine whether risk factors associated with obesity are influenced by genetic variation of apolipoprotein E (ApoE). Methods: 81 obese children (mean age 9.4 ± 2.8 years) and an age-matched control group were included. Body composition, lipid profile, and glucose and insulin levels were evaluated according to international recommendations, and the blood pressure was measured by an oscillometric method. Results: The calculated frequencies of the ApoE alleles *2, *3, and *4 (0.04, 0.88 and 0.08) in obese children were similar to those of eutrophic age-matched controls (0.07, 0.82, and 0.11) and fitted the range of variation generally observed in southern European populations. Age, anthropometric parameters, body fat mass, and blood pressure were similar in E2/3, E3/3 and E4/3 genotypes. Total/high-density lipoprotein cholesterol and low-density lipoprotein/high-density lipoprotein cholesterol ratios were higher in the E4/3 group as compared with E3/3 (p < 0.01) and E2/3 (p < 0.05) groups. No differences concerning clusters of risk factors were observed among the three genotypes. No associations were found between ApoE polymorphism and glucose levels (fasting and at 2 h) and between fasting insulin levels and HOMA_IR results. Higher levels of fasting and 2-hour insulin and higher HOMA_IR values were significantly associated with a higher fat mass. Conclusions: ApoE polymorphism seems to influence some lipid profile abnormalities associated with obesity in childhood. However, clustering of risk factors and insulin resistance seem not to be dependent on ApoE polymorphism.