Introduction Down syndrome (DS) is associated with various congenital anomalies and metabolic alterations, such as dyslipidemias, that can lead to cardiovascular disease in adulthood. This study was designed to describe the lipid concentrations and the frequency of dyslipidemias in children with DS. Materials and methods The sample included 386 patients, 52.4% male. The study was carried out on children with DS, aged 2–18 years old, who were patients at the Mexican National Institute of Pediatrics between May 2016 and June 2017. Their height and weight were recorded, and their serum cholesterol, HDL cholesterol, and triglyceride levels were determined. Results Of the total patients included, 57.5% had some type of dyslipidemia, 32.6% isolated and 24.9% combined. The most common alteration, considering both isolated and combined dyslipidemias, was low HDL, in 45.9%, followed by hypertriglyceridemia, in 26.2%. Among those with combined dyslipidemia, high TG with low HDL-c was the most common, in 17.9%. A significant association was found between dyslipidemia and obesity, as well as between dyslipidemia and central obesity. The percentiles of lipid values are reported. Conclusion The presence of an unfavorable lipid profile is common in pediatric patients with Down syndrome, especially low HDL cholesterol and high triglycerides.