Immunology is a challenging topic to teach due to its complexity of cellular interactions and regulatory mediators involved. Students can find it overwhelming and lose sight of key concepts and there is a need for inclusion of teaching methods which increase engagement and stimulate active learning. Simulation of clinical scenarios using high-fidelity manikins is a teaching method used successfully in clinical teaching. Our aim was to determine whether this method could be adapted to enhance the learning experience of medical science students studying Immunology. The scenario chosen for this study was sepsis as it provides an example of a real-life problem where immune system responses drive clinical outcome. The class was tested on seven students taking an Applied Immunology course and this was their first exposure to a clinical simulator. They all had fundamental knowledge of the inflammatory response to bacteria from lectures and the class was designed to encourage them to use this knowledge to identify the problem and improve the outcome. The students took part in three iterations of the same five minute scenario in which a 68-year-old male arrived in the A&E department with chief complaints of weakness, dizziness and fever and showing vital signs and lab test results consistent with sepsis. After each iteration there was an interactive discussion. Initially, with discussion, the students were able to offer a primary diagnosis of sepsis and suggested additional tests to confirm the diagnosis. After the second, in which a blood culture was shown to be positive for gram-negative bacteria and the patient had deteriorated, the students suggested the administration of a wide-spectrum antibiotic and high-volume fluid as treatment. These were administered in the third scenario which showed some improvement of the patient. A final review and discussion covered alternative outcomes and the inflammatory mechanisms and cytokines involved. The students were then asked to complete an anonymous evaluation of the class. They were asked to rate ten statements on a five-point scale where five is the highest. All the students responded that their knowledge of sepsis had improved and six out of seven that their knowledge of inflammation had improved. They all agreed that the class had improved their problem solving skills. They said that it was a ‘cool’ way to learn and free comments included ‘It was good to think of immunology in real life simulation…’ and ‘this helped seeing how different factors can affect patients which encouraged thinking…’. We concluded that clinical simulation could be used effectively to improve student engagement in a complex immunology topic. This active learning process improved their understanding and consolidated knowledge. The novel use of clinical high-fidelity manikins will be helpful for teaching other complex topics in Immunology and could be applied to other medical science subjects.