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Generalized Social Anxiety Disorder (GSAD) is characterized by excessive fear and avoidance of several types of social and performance situations. The pathophysiology is not well understood, but research in animals and humans has provided evidence that oxytocin helps regulate normal social affiliative behavior. Previous work in healthy male subjects demonstrated a rise in plasma oxytocin after receiving a high trust signal. To examine the oxytocin system in GSAD, we measured plasma oxytocin in GSAD patients and controls, before and after the social “Trust Game,” a neuroeconomic test examining trust behavior and reaction to trust using real monetary incentives.Thirty-nine subjects with GSAD and 28 healthy controls provided three blood samples for oxytocin measurement before the Trust Game, and one sample after the game. Plasma estradiol was also measured at baseline. The Trust Game protocol version prioritized the sending of a signal of high cooperation and trust to all participants. All analyses controlled for gender and estradiol levels.Mean oxytocin levels post-Trust Game (P= .025), and overall (area under the curve,P= .011) were lower in GSADpatients compared to controls, after controlling for sex and estradiol. There was no significant change in oxytocin levels after the game in either group.We report low plasma oxytocin levels in patients with GSAD during a prosocial laboratory task paradigm. Additional research will be important to further examine the relationship between oxytocin and social behavior in GSAD.