The serotonergic system and more precisely the type 2A serotonin receptor (5-HT2AR) is involved in a wide variety of cognitive and emotional functions. Specifically, the social impairments observed in different psychiatric disorders, such as schizophrenia and Asperger’s syndrome, have been linked with a hypofunction of 5-HT2AR. However, the mechanisms underlying this phenotype remain unclear. In this study we analyze the role of 5-HT2AR in social preference and dominance using a genetically modified mouse model that presents a constitutive deletion of 5-HT2AR (KO) compared to conspecific wild type (WT). For this purpose, we use the three-chamber social interaction test (SI) and the dominance tube (TD). We also explore the role of this receptor in the prefrontal cortex in social behavior by infusing adult WT animals with a selective 5-HT2AR antagonist (MDL) prior to the social interaction test. Male and female KO mice had lower social preference compared to WT mice, and genotype was a strong predictor of matches won in duels in the TD. Furthermore, the acute administration of MDL in the mPFC of WT mice had no effect on the SI suggesting that the receptor is necessary during development for the animals to demonstrate normal social behavior but is not recruited during the task. Moreover, preliminary SI results from animals that selectively express 5-HT2AR in the cortex suggest that the apparent developmental role of the receptor might be mediated by its expression in the cortex.