Limited research is available on the frequency of spiritual distress and its relationship with physical and emotional distress. We reviewed patients admitted to our acute palliative care unit (APCU) and determined the association between patient characteristics, symptom severity using the Edmonton Symptom Assessment scale (ESAS), and spiritual distress as reported by a chaplain on initial visit. In all, 50 (44%) of 113 patients had spiritual distress. In univariate analysis, patients with spiritual distress were more likely to be younger (odds ratio [OR] = 0.96, P = .004), to have pain (OR = 1.2, P = .010) and depression (OR = 1.24, P = .018) compared to those without spiritual distress. Spiritual distress was associated with age (OR = 0.96, P = .012) and depression (OR = 1.27, P = .020) in multivariate analysis. Our findings support regular spiritual assessment as part of the interdisciplinary approach to optimize symptom control.