Down syndrome (DS) is the most common chromosomal disorder causing mental retardation with a worldwide average prevalence of 1-2 cases per 1000 births. This study aimed to determine the comorbidities associated with DS and the coverage of health care services and developmental interventions for DS livebirths in Southern Thailand. A total of 149 livebirth DS infants, recruited through the prospective birth defects registry system during 2009-2013 in 3 provinces in Southern Thailand, were regularly followed-up every 3-6 months. The data collection form included the infants' demographic data, associated congenital anomalies, and developmental interventions. The DS infants were born at an average gestational age of 38.5 +/- 2.3 weeks with average birth weight of 2760 +/- 478 g, length 48.5 +/- 2.2 cm, and head circumference 32.7 +/- 1.2 cm. Congenital heart diseases, gastrointestinal defects and congenital hypothyroidism were found in 43.0%, 6.7%, and 12.1% of the cases, respectively. The percentage of DS infants who received developmental interventions in this current study were significantly greater than in a previous study covering the years 1992-2002: early stimulation program 90.0% vs. 65.6% (P < 0.01), and speech training program 74.8% vs. 38.9% (P < 0.01), respectively, and the infants in our study began intervention programs significantly earlier, 0.58 +/- 0.39 years vs. 1.69 +/- 0.66 years, respectively. Congenital heart disease was the most common comorbidity associated with DS. The coverage of health care services and developmental interventions for DS children has generally improved in Southern Thailand. One hundred percent coverage of health services and interventions for children with special needs is expected in the near future.