ObjectiveStigma can create divisions within societies, hindering social cohesion and cooperation. Notably, it has significant public health implications, especially during infectious disease outbreaks like COVID-19. However, little is known about the neural and molecular basis of disease-related stigma and their association with individual differences. MethodsTo address this gap, we performed a double-blind, placebo-controlled, within-subject design study with 70 males, to investigate the effect of intranasal oxytocin (OT) administration on the explicit and implicit processing of disease-related stigma (i.e., COVID-19 stigma). After self-administrated 24 IU of OT or placebo, participants completed a stigma evaluation task and an Implicit Association Test (IAT) to assess the explicit and implicit processes of stigma evaluation, respectively. ResultsThe results showed that oxytocin amplified the differences between participants with high and low social anxiety in explicit COVID-19 stigma, with a higher inclination to attribute the stigmatized status of the stigmatized targets (i.e., COVID-19 related group) to personal causes in high social anxiety individuals, but reduced blame towards the stigmatized targets in low social anxiety individuals under oxytocin compared to placebo treatment. Furthermore, oxytocin strengthened the connections between responsibility attribution and the other processes (i.e., emotional, approach motivation, social deviance). While no modulation of oxytocin on implicit stigma emerged, oxytocin did modulate the associations between specific dimensions of explicit stigma (i.e., social deviance and approach motivation) and implicit stigma. ConclusionIn conclusion, these findings demonstrated that intranasal oxytocin administration could temporally impact the explicit cognitive judgment in disease-related stigma but not the implicit aspect; furthermore, it modulated in distinct ways in individuals with different levels of social anxiety. These findings highlight the trait-dependent oxytocin modulation on disease-related stigma, implying that oxytocin is partly involved in the endocrine system of disease-related stigma. By unraveling the molecular basis of stigma and its association with individual traits, such as social anxiety, we can tailor interventions to meet specific needs of different individuals in the future.