The hormone oxytocin is known to play a role in social relationships and bonding, yet it has been relatively unexplored in relation to psychosocial variables. Thus, the aim of this study was to determine whether associations exist among oxytocin and the psychological resource factors spirituality, benefit finding, coping, and optimism, as well as depression and anxiety, in a diverse HIV-positive sample. Interviews and questionnaires were administered to 79 HIV-positive individuals, 38 of whom were from a chronic disease sample, and 41 of whom were from a study investigating spiritual transformation. Plasma samples were collected and assayed for oxytocin after being purified by an extraction procedure. Higher oxytocin levels were significantly associated with greater spirituality (r = .27, n = 79, p = .017), spiritual transformation (r = .26, n = 79, p = .020) and benefit finding (r = .32, n = 77, p = .005). Median oxytocin levels of those who experienced a spiritual transformation (26.48 pg/ml) were two times higher (U = 507, p = .021) than those who did not undergo a spiritual transformation (13.13 pg/ml). Oxytocin levels were not associated with coping, optimism, depression, or anxiety in this sample. The psychological resource factors spirituality and benefit finding were found to be associated with increased levels of oxytocin, suggesting that future studies should examine whether this hormone may play a protective role in HIV/AIDS, perhaps by mediating the relationship between these resource-related factors and health outcomes.