Background Faith and belief systems impact the emotional as well as immunological states of believers in ways that we are just beginning to understand. However, the clinical implications of prior studies are limited. The aim of the HEALING (Hospital-based Ecumenical and Linguistic Immuno-NeuroloGic) study is to examine immunological and neurological changes in hospitalized patients after meeting with a chaplain coupled with the study of biblical readings. Methods Hospitalized patients were pre-screened to identify those who were most in need of a spiritual intervention. A passage from the Bible was read to them during a meeting with the chaplain at bedside (n = 20) or in the chapel (n = 18). No meeting occurred in the randomized control group (n = 19). Blood samples were obtained 30 min prior and 60 min after the meeting to measure white blood cell (WBC) count, interferon-gamma (IFN-γ), immunoglobulin M (IgM), IgA, IgG, and complement 3 (C3). A subgroup of the visited patients was subjected to functional magnetic resonance imaging (fMRI), during which they listened to an audiotape of readings of the same biblical passage (n = 21). Results Immunological changes were not significant. Conversely, a significant (pfwe = 0.003) correlation was observed between lymphocyte changes and activation of the angular gyrus (left BA39) during fMRI, a brain area involved in word recognition. Conclusions This article contributes to the relevant literature by helping to create a realistic picture of the possibilities of neuroimmune modulation in clinical practice. Compared to healthy volunteers, the extent of short-term neuroimmunomodulation becomes narrower in a clinical setting. Although limited by the sample size and cohort study design, the findings suggest that the depth of psycho-immunological changes could depend on the degree to which the chaplain’s main message is understood.