<b><i>Background:</i></b> The neuropeptides oxytocin and vasopressin play a central role in social behavior. Trials with intranasal oxytocin have been conducted and many indicate that the hormone facilitates affiliative behavior and trust. Intranasal oxytocin administration is suggested as a treatment option for psychiatric illnesses with altered sociability as a core symptom and the effects may be due to differences in variants of oxytocin- and vasopressin-related genes. The purpose of the present study was to investigate the endogenous oxytocin system by exploring the relationship between variants in the oxytocin gene factors and personality traits closely related to trust, anxiety and social behavior. <b><i>Methods:</i></b> 72 single nucleotide polymorphisms (SNPs) in the genes coding for oxytocin (OXT), vasopressin (AVP), the oxytocin receptor (OXTR) and CD38 (CD38), including polymorphisms reported earlier to be related to social phenotypes and novel SNPs, were investigated in 196 healthy subjects. Association analysis between these variants and 3 personality traits (agreeableness, neuroticism and extraversion) measured by the Neuroticism-Extraversion-Openness Five-Factor Inventory was performed. <b><i>Results:</i></b> We found 7 nominally significant associations for personality traits: agreeableness [rs857240 (AVP, p = 0.0075), rs2270463 (OXTR, p = 0.047)], neuroticism [rs3756242 (CD38, p = 0.024), rs13104011 (CD38, p = 0.024), rs6816486 (CD38, p = 0.024), rs7655635 (CD38, p = 0.034)] and extraversion [rs237878 (OXTR, p = 0.019)]. None of these associations remained significant after the Bonferroni correction (p threshold = 2.31 × 10^-4). <b><i>Conclusion:</i></b> Our results do not contradict the hypothesis of associations between personality traits and oxytocin-related gene variants; however, there are no statistically significant associations after correcting for multiple testing, warranting replication in larger samples.