Abstract Background In occupational therapy, empathy is a fundamental concept and has a positive impact on health and quality of care outcomes for patients. It is a basic and essential concept that should prevail in the training of occupational therapy students. The aim of this study is to validate and cross-culturally adapt the Jefferson Medical Empathy Scale, version for health professionals (JSE-HPS) in a sample of Spanish university students of occupational therapy. Methods A cross-sectional descriptive study was conducted between 2019 and 2020. A convenience sample was selected, consisting of 221 students from the four courses of the Occupational Therapy degree at the Universidad Rey Juan Carlos during the 2019–20 academic year. Each of the participants voluntarily and anonymously completed a sociodemographic data sheet (including age and sex), in addition to the following assessment scales: JSE-HPS and the Interpersonal Reactivity Index (IRI). Results A culturally adapted version of the JSE-HPS that guarantees conceptual and grammatical equivalence specific to the study population was obtained. The psychometric analysis of the translated version showed a Cronbach coefficient α of 0.786. The test-retest reliability analysis showed an intraclass correlation coefficient of 0.90 (95% CI = 0.86–0.93, p < 0.0001). Confirmatory factor analysis (CFA) showed positive results (χ² = 269.095, df = 167, p < 0.001, Confirmatory Fit Index [CFI] = 0.90, Root Mean Square Error of Approximation [RMSEA] = 0.04). Conclusion The cultural adaptation and psychometric results suggest that the Spanish version of the JSE-HPS is a valid and reliable way to evaluate the empathic ability of occupational therapy students.