Social behavior (SB) is defined as interactions among individuals that offer mutual benefits and comprise different actions. Deficits in SB are a hallmark of different psychiatric disorders, including autism spectrum disorders. Changes in 5-HT levels, as well as some activity of key molecules within the system have been associated with deficits in SB. Serotonin 2A receptors (5-HT2aR) are one of the main excitatory serotonergic receptors. Social deficits in humans were associated with 5-HT2aR hypofunction. Interestingly, 5-HT2aR agonists increase social interaction (SI) in humans and animal models suggesting that 5-HT2aR might modulate SB. We used genetically modified male and female mice (htr2a-/-) and their littermates’ controls (htr2a+/+) to study the specific role of the receptor in SB. P90 or older animals were exposed to different behavioral paradigms. In the three-chambers SI test htr2a-/- male and female mice show decreased discrimination indexes compared with same sex htr2+/+ mice. Moreover, this deficit was rescued by the genetic restoration of the 5-HT2aR expression in the cortex suggesting a specific role of the receptor in this area. However, pharmacological manipulations in htr2+/+ adult mice before the SI test showed no effect suggesting that 5-HT2aR is not acutely recruited for SB. Taken together, these results suggest that 5-HT2aR has a role in SB and its involvement appears to be due to a developmental or chronic action.