This research questions whether open innovation can enhance the organisational resilience of United Kingdom life science small and medium-sized enterprises, by asking how the two concepts are related and influenced. This provides a significant and original contribution to knowledge and practice, to best understand how the two concepts associate, and how practitioners should allocate their limited resources across three factors (internal, demographic, external) to enhance both concepts together. The rationale is drawn from a gap in the peer-reviewed and grey literature, as it reports that United Kingdom life science small and medium-sized enterprises face a 39% failure rate, with those practicing closed innovation being more at risk. These sized enterprises represent 99.9% of the national economy and those operating in the life sciences must become resilient to deliver important social health and economic benefits. This research contributes to the body of knowledge by first considering the concept of organisational resilience, which has a standardised industry definition as an ability to anticipate, prepare for, respond, and adapt to disruption and change. The second concept of this research, open innovation, is defined as using external resources for innovation, whilst also allowing any unused resources to go outside of organisational boundaries. Mixed methods with multi-stage validation of regression and thematic analyses, ensured rigour. Findings show a moderate, positive relationship between the concepts for United Kingdom life science small and medium-sized enterprises. It was, therefore, of value to combine them into an interaction variable, to measure their influences. The foremost contribution is that internationalisation is the most significant influence, implying that a globalised outlook is beneficial. Furthermore, the frequency of significant influences was equal across internal and external factors, indicating that owner-managers should be considerate of both contexts during their resource-based activities.