The purpose of the current study is to investigate the extent to which mindfulness (observing and describing), dispositional optimism and personal meaning are associated with self-efficacy for managing a chronic disease (SEMCD) among 57 people living with HIV in the DFW Metroplex. Several statistical analyses, including a hierarchical linear regression analysis, were conducted. Results indicate, after controlling for age and gender, the overall model accounted for a significant proportion of the variance (adjusted R2 = .39) in self-efficacy for managing chronic disease, F (6, 50) = 5.80, p < .01. Both subscales of mindfulness were significantly related to self-efficacy. However, observing was negatively, associated with SEMCD (β = -0.44, p < .05), and describing was positively associated with self-efficacy (β = 0.60, p < .01). As a result, incorporating these mindfulness skills into self-efficacy based self-management programs may greatly improve self-management, thus positively influencing psychological and physiological health outcomes that are essential to the health and wellbeing of people living with HIV/AIDS. Future research should investigate methods of manipulating observing and describing, and determine what proficiency in these skills is most beneficial to improve self-efficacy.