Obstructive sleep apnea syndrome (OSAS) is one of the most complex disorders of sleep; it involves several genetic factors that contribute to the phenotype. Serotonin (5-HT) regulates a variety of visceral and physiological functions, including sleep. Gene 5-HTR2A polymorphisms may change the transcription of several receptors in the serotoninergic system, thereby contributing to OSAS. Aim To investigate the prevalence of T102C and -1438G/A polymorphisms in the 5-HTR2A gene of patients with and without OSAS. Material and Method A molecular study of 100 index-cases and 100 controls of both genders. DNA was extracted from blood leukocytes samples and the regions that enclose both polymorphisms were amplified with PCR-RFLP. Study design A cross-sectional case study. Results There was a significant prevalence of males in index cases compared to controls (p<0.0001). No significant genotypic differences between cases and controls were found in T102C polymorphisms ( p =1.000). There were significant differences between the AA genotype of -1438G/A polymorphisms and patients with OSAS (OR:2.3; CI95%:1.20-4.38, p =0.01). Conclusion Serotonergic mechanisms may be related to OSAS. There were no differences in the prevalence of T102C polymorphisms in patients with OSAS and the control group. There is evidence of an association between the -1438G/A polymorphism and OSAS.