Across their lifespans, and in many clinical settings, patients have spiritual care needs. Many nurses lack competence related to providing spiritual care. Popular educational strategies, such as simulated educational programs and objective structured clinical examinations (OSCE), have not been widely adopted in nursing spiritual care education. The purpose of this study was to explore the effects of a scenario-based spiritual care course on spiritual care competence in nurses. This quasi-experimental study employed a repeated-measures pre-test/post-test design with assessments immediately before, immediately after, and 3 months post-intervention. Nurses providing direct patient care in diverse clinical settings were recruited from a large medical foundation in northern Taiwan. The intervention was a one day scenario-based spiritual care course and OSCE. The experimental group (n = 53) and controls (n = 85) were matched for their similar units, ages, working experience, and clinical ladder status. The Spiritual Care Competence Scale (SCCS), Spiritual Perspective Scale (SPS), Spiritual Care Perspective Scale-Revised (SCPS-R), and reflection logs were completed by both experimental and control groups. The Course Satisfaction Scale, OSCE Checklist, and Standardized Patient Feedback Scale (SPFS) were completed by the experimental group only. The experimental group had significantly higher SPS scores and self-evaluated SCCS scores, and lower SCPS-R scores (more positive spiritual perspectives), than controls at 3 months post-intervention. The experimental group showed significant within-subject effects at three time points on SPS scores, SCPS-R scores, and self-evaluated SCCS scores. Mean global performance of OSCE was 3.40 ± 0.91, and SP feedback indicated strengths and areas for improvement. In conclusion, the scenario-based spiritual care course effectively enhanced nurses’ spiritual care competence, competence, and skills. Blended education techniques can therefore enhance nurses’ ability to support patients with spiritual care needs.