Background: Nursing is an emotionally demanding and physically draining occupation. Well-being of health care workers is essential to achieve success in care and have good cooperation relationships with other health professionals. Objective: The purpose of this study was to evaluate the effectiveness of a light-based intervention on perceived nursing-related stress in health care personnel working in an operating room environment. Methods: A total of 84 nurses participated in this randomized, cross-over controlled study. Intervention consisted of 4 weeks of bright blue-enriched light exposure using a LED head-mounted portable device (n = 42) or no light exposure (n = 42) separated by a 2-week washout period in a crossover fashion. Participants completes questionnaires for the Nursing Stress Scale (NSS). Results: Intervention and control groups were comparable in terms of demographics, with a median age of 34 (IQR: 27-49) and 69 (82%) female. The mean baseline NSS score was similar in both groups before intervention. The NSS score of the intervention group was significantly lower after intervention than the baseline score: the NSS score difference before and after intervention was 15.1 (SD 7.6) (p < 0.001) and 19.7 (SD 7.5) (p < 0.001) during the two successive periods of intervention, respectively. The cross-group comparison after intervention showed a significantly higher NSS score difference after intervention in the intervention group than the control group: 15.1 (SD 7.6) vs. 1.4 (SD 8.4) (p < 0.001) and 19.7 (SD 7.5) vs. 1.7 (SD 8.9) (p < 0.001) during the two successive periods of intervention, respectively. Conclusion: Alternative person-directed initiatives should be considered to improve the well-being of the health workforce in operating rooms, especially during the coronavirus pandemic.